Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy and Study Selection
2.2. Data Extraction
3. Results
3.1. Literature Search and Study Selection
3.2. Gene Alteration Frequency in PDAC Patients
3.3. Types of Variants Identified in HRR Genes (ATM, BRCA1, BRCA2, PALB2)
3.4. Types of Variants Identified in MMR Genes (EPCAM, MLH1, MSH2, MSH6, and PMS2)
3.5. Types of Variants Identified in Other Cancer–Related Genes (CDKN2A, STK11, TP53)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2022. CA Cancer J. Clin. 2022, 72, 7–33. [Google Scholar] [CrossRef] [PubMed]
- Park, W.; Chawla, A.; O’Reilly, E.M. Pancreatic Cancer: A Review. JAMA 2021, 326, 851. [Google Scholar] [CrossRef] [PubMed]
- GBD 2017 Pancreatic Cancer Collaborators. The Global, Regional, and National Burden of Pancreatic Cancer and Its Attributable Risk Factors in 195 Countries and Territories, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol. Hepatol. 2019, 4, 934–947. [CrossRef] [PubMed]
- Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [Google Scholar] [CrossRef] [PubMed]
- Singhi, A.D.; Koay, E.J.; Chari, S.T.; Maitra, A. Early Detection of Pancreatic Cancer: Opportunities and Challenges. Gastroenterology 2019, 156, 2024–2040. [Google Scholar] [CrossRef] [PubMed]
- Ren, Y.; Wang, S.; Wu, B.; Wang, Z. Clinicopathological Features, Prognostic Factors and Survival in Patients with Pancreatic Cancer Bone Metastasis. Front. Oncol. 2022, 12, 759403. [Google Scholar] [CrossRef]
- Argentiero, A.; Calabrese, A.; Solimando, A.G.; Notaristefano, A.; Panarelli, M.M.G.; Brunetti, O. Bone Metastasis as Primary Presentation of Pancreatic Ductal Adenocarcinoma: A Case Report and Literature Review. Clin. Case Rep. 2019, 7, 1972–1976. [Google Scholar] [CrossRef]
- Klatte, D.C.F.; Boekestijn, B.; Onnekink, A.M.; Dekker, F.W.; van der Geest, L.G.; Wasser, M.N.J.M.; Feshtali, S.; Mieog, J.S.D.; Luelmo, S.A.C.; Morreau, H.; et al. Surveillance for Pancreatic Cancer in High-Risk Individuals Leads to Improved Outcomes: A Propensity Score-Matched Analysis. Gastroenterology 2023, 164, 1223–1231.e4. [Google Scholar] [CrossRef]
- Halbrook, C.J.; Lyssiotis, C.A.; Pasca di Magliano, M.; Maitra, A. Pancreatic Cancer: Advances and Challenges. Cell 2023, 186, 1729–1754. [Google Scholar] [CrossRef]
- Pilarski, R. The Role of BRCA Testing in Hereditary Pancreatic and Prostate Cancer Families. Am. Soc. Clin. Oncol. Educ. Book 2019, 39, 79–86. [Google Scholar] [CrossRef]
- Chaffee, K.G.; Oberg, A.L.; McWilliams, R.R.; Majithia, N.; Allen, B.A.; Kidd, J.; Singh, N.; Hartman, A.-R.; Wenstrup, R.J.; Petersen, G.M. Prevalence of Germline Mutations in Cancer Genes among Pancreatic Cancer Patients with Positive Family History. Genet. Med. 2018, 20, 119–127. [Google Scholar] [CrossRef] [PubMed]
- Klatte, D.C.F.; Wallace, M.B.; Löhr, M.; Bruno, M.J.; van Leerdam, M.E. Hereditary Pancreatic Cancer. Best Pract. Res. Clin. Gastroenterol. 2022, 58–59, 101783. [Google Scholar] [CrossRef] [PubMed]
- Klatte, D.C.F.; Boekestijn, B.; Wasser, M.N.J.M.; Feshtali Shahbazi, S.; Ibrahim, I.S.; Mieog, J.S.D.; Luelmo, S.A.C.; Morreau, H.; Potjer, T.P.; Inderson, A.; et al. Pancreatic Cancer Surveillance in Carriers of a Germline CDKN2A Pathogenic Variant: Yield and Outcomes of a 20-Year Prospective Follow-Up. J. Clin. Oncol. 2022, 40, 3267–3277. [Google Scholar] [CrossRef] [PubMed]
- Kindler, H.L.; Yoo, H.K.; Hettle, R.; Cui, K.Y.; Joo, S.; Locker, G.Y.; Golan, T. Patient-Centered Outcomes in the POLO Study of Active Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. Cancer 2023, 129, 1411–1418. [Google Scholar] [CrossRef] [PubMed]
- Crowley, F.; Gandhi, S.; Rudshteyn, M.; Sehmbhi, M.; Cohen, D.J. Adherence to NCCN Genetic Testing Guidelines in Pancreatic Cancer and Impact on Treatment. Oncology 2023, 28, 486–493. [Google Scholar] [CrossRef]
- Stoffel, E.M.; McKernin, S.E.; Brand, R.; Canto, M.; Goggins, M.; Moravek, C.; Nagarajan, A.; Petersen, G.M.; Simeone, D.M.; Yurgelun, M.; et al. Evaluating Susceptibility to Pancreatic Cancer: ASCO Provisional Clinical Opinion. J. Clin. Oncol. 2019, 37, 153–164. [Google Scholar] [CrossRef]
- Page, M.J.; McKenzie, J.E.; Bossuyt, P.M.; Boutron, I.; Hoffmann, T.C.; Mulrow, C.D.; Shamseer, L.; Tetzlaff, J.M.; Akl, E.A.; Brennan, S.E.; et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ 2021, 372, n71. [Google Scholar] [CrossRef]
- Golan, T.; O’Kane, G.M.; Denroche, R.E.; Raitses-Gurevich, M.; Grant, R.C.; Holter, S.; Wang, Y.; Zhang, A.; Jang, G.H.; Stossel, C.; et al. Genomic Features and Classification of Homologous Recombination Deficient Pancreatic Ductal Adenocarcinoma. Gastroenterology 2021, 160, 2119–2132.e9. [Google Scholar] [CrossRef]
- Shindo, K.; Yu, J.; Suenaga, M.; Fesharakizadeh, S.; Cho, C.; Macgregor-Das, A.; Siddiqui, A.; Witmer, P.D.; Tamura, K.; Song, T.J.; et al. Deleterious Germline Mutations in Patients with Apparently Sporadic Pancreatic Adenocarcinoma. JCO 2017, 35, 3382–3390. [Google Scholar] [CrossRef]
- Puccini, A.; Ponzano, M.; Dalmasso, B.; Vanni, I.; Gandini, A.; Puglisi, S.; Borea, R.; Cremante, M.; Bruno, W.; Andreotti, V.; et al. Clinical Significance of Germline Pathogenic Variants among 51 Cancer Predisposition Genes in an Unselected Cohort of Italian Pancreatic Cancer Patients. Cancers 2022, 14, 4447. [Google Scholar] [CrossRef]
- Lowery, M.A.; Wong, W.; Jordan, E.J.; Lee, J.W.; Kemel, Y.; Vijai, J.; Mandelker, D.; Zehir, A.; Capanu, M.; Salo-Mullen, E.; et al. Prospective Evaluation of Germline Alterations in Patients with Exocrine Pancreatic Neoplasms. JNCI J. Natl. Cancer Inst. 2018, 110, 1067–1074. [Google Scholar] [CrossRef] [PubMed]
- Hu, C.; LaDuca, H.; Shimelis, H.; Polley, E.C.; Lilyquist, J.; Hart, S.N.; Na, J.; Thomas, A.; Lee, K.Y.; Davis, B.T.; et al. Multigene Hereditary Cancer Panels Reveal High-Risk Pancreatic Cancer Susceptibility Genes. JCO Precis. Oncol. 2018, 2, 1–28. [Google Scholar] [CrossRef] [PubMed]
- Astiazaran-Symonds, E.; Kim, J.; Haley, J.S.; Kim, S.Y.; Rao, H.S.; Genetics Center, R.; Carey, D.J.; Stewart, D.R.; Goldstein, A.M. A Genome-First Approach to Estimate Prevalence of Germline Pathogenic Variants and Risk of Pancreatic Cancer in Select Cancer Susceptibility Genes. Cancers 2022, 14, 3257. [Google Scholar] [CrossRef] [PubMed]
- Antwi, S.O.; Fagan, S.E.; Chaffee, K.G.; Bamlet, W.R.; Hu, C.; Polley, E.C.; Hart, S.N.; Shimelis, H.; Lilyquist, J.; Gnanaolivu, R.D.; et al. Risk of Different Cancers Among First-Degree Relatives of Pancreatic Cancer Patients: Influence of Probands’ Susceptibility Gene Mutation Status. JNCI J. Natl. Cancer Inst. 2019, 111, 264–271. [Google Scholar] [CrossRef]
- Xiong, A.; Ma, N.; Wei, G.; Li, C.; Li, K.; Wang, B. Genomic Alterations in Tumor Tissue and ctDNA from Chinese Pancreatic Cancer Patients. Am. J. Cancer Res. 2021, 11, 4551–4567. [Google Scholar]
- Chittenden, A.; Haraldsdottir, S.; Ukaegbu, C.; Underhill-Blazey, M.; Gaonkar, S.; Uno, H.; Brais, L.K.; Perez, K.; Wolpin, B.M.; Syngal, S.; et al. Implementing Systematic Genetic Counseling and Multigene Germline Testing for Individuals with Pancreatic Cancer. JCO Oncol. Pract. 2021, 17, e236–e247. [Google Scholar] [CrossRef]
- Cremin, C.; Lee, M.K.; Hong, Q.; Hoeschen, C.; Mackenzie, A.; Dixon, K.; McCullum, M.; Nuk, J.; Kalloger, S.; Karasinska, J.; et al. Burden of Hereditary Cancer Susceptibility in Unselected Patients with Pancreatic Ductal Adenocarcinoma Referred for Germline Screening. Cancer Med. 2020, 9, 4004–4013. [Google Scholar] [CrossRef]
- Dal Buono, A.; Poliani, L.; Greco, L.; Bianchi, P.; Barile, M.; Giatti, V.; Bonifacio, C.; Carrara, S.; Malesci, A.; Laghi, L. Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients with Pancreatic Cancer or Suspected Related Hereditary Syndromes: Historical Prospective Analysis. Cancers 2023, 15, 1852. [Google Scholar] [CrossRef] [PubMed]
- Hu, C.; Hart, S.N.; Polley, E.C.; Gnanaolivu, R.; Shimelis, H.; Lee, K.Y.; Lilyquist, J.; Na, J.; Moore, R.; Antwi, S.O.; et al. Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer. JAMA 2018, 319, 2401. [Google Scholar] [CrossRef]
- Mizukami, K.; Iwasaki, Y.; Kawakami, E.; Hirata, M.; Kamatani, Y.; Matsuda, K.; Endo, M.; Sugano, K.; Yoshida, T.; Murakami, Y.; et al. Genetic Characterization of Pancreatic Cancer Patients and Prediction of Carrier Status of Germline Pathogenic Variants in Cancer-Predisposing Genes. eBioMedicine 2020, 60, 103033. [Google Scholar] [CrossRef] [PubMed]
- Rabe, K.G.; Stevens, M.A.; Hernández, A.T.; Chandra, S.; Hubbard, J.M.; Kemppainen, J.L.; Majumder, S.; Petersen, G.M. Pancreatic Cancer Risk to Siblings of Probands in Bilineal Cancer Settings. Genet. Med. 2022, 24, 1008–1016. [Google Scholar] [CrossRef] [PubMed]
- Yin, L.; Wei, J.; Lu, Z.; Huang, S.; Gao, H.; Chen, J.; Guo, F.; Tu, M.; Xiao, B.; Xi, C.; et al. Prevalence of Germline Sequence Variations Among Patients with Pancreatic Cancer in China. JAMA Netw. Open 2022, 5, e2148721. [Google Scholar] [CrossRef] [PubMed]
- Slavin, T.P.; Neuhausen, S.L.; Nehoray, B.; Niell-Swiller, M.; Solomon, I.; Rybak, C.; Blazer, K.; Adamson, A.; Yang, K.; Sand, S.; et al. The Spectrum of Genetic Variants in Hereditary Pancreatic Cancer Includes Fanconi Anemia Genes. Fam. Cancer 2018, 17, 235–245. [Google Scholar] [CrossRef] [PubMed]
- Takai, E.; Yachida, S.; Shimizu, K.; Furuse, J.; Kubo, E.; Ohmoto, A.; Suzuki, M.; Hruban, R.H.; Okusaka, T.; Morizane, C.; et al. Germline Mutations in Japanese Familial Pancreatic Cancer Patients. Oncotarget 2016, 7, 74227–74235. [Google Scholar] [CrossRef] [PubMed]
- Takai, E.; Nakamura, H.; Chiku, S.; Kubo, E.; Ohmoto, A.; Totoki, Y.; Shibata, T.; Higuchi, R.; Yamamoto, M.; Furuse, J.; et al. Whole-Exome Sequencing Reveals New Potential Susceptibility Genes for Japanese Familial Pancreatic Cancer. Ann. Surg. 2022, 275, e652–e658. [Google Scholar] [CrossRef] [PubMed]
- Smith, A.L.; Wong, C.; Cuggia, A.; Borgida, A.; Holter, S.; Hall, A.; Connor, A.A.; Bascuñana, C.; Asselah, J.; Bouganim, N.; et al. Reflex Testing for Germline BRCA1, BRCA2, PALB2, and ATM Mutations in Pancreatic Cancer: Mutation Prevalence and Clinical Outcomes from Two Canadian Research Registries. JCO Precis. Oncol. 2018, 2, 1–16. [Google Scholar] [CrossRef] [PubMed]
- Hutchings, D.; Jiang, Z.; Skaro, M.; Weiss, M.J.; Wolfgang, C.L.; Makary, M.A.; He, J.; Cameron, J.L.; Zheng, L.; Klimstra, D.S.; et al. Histomorphology of Pancreatic Cancer in Patients with Inherited ATM Serine/Threonine Kinase Pathogenic Variants. Mod. Pathol. 2019, 32, 1806–1813. [Google Scholar] [CrossRef] [PubMed]
- Goldstein, J.B.; Zhao, L.; Wang, X.; Ghelman, Y.; Overman, M.J.; Javle, M.M.; Shroff, R.T.; Varadhachary, G.R.; Wolff, R.A.; McAllister, F.; et al. Germline DNA Sequencing Reveals Novel Mutations Predictive of Overall Survival in a Cohort of Patients with Pancreatic Cancer. Clin. Cancer Res. 2020, 26, 1385–1394. [Google Scholar] [CrossRef]
- Walker, E.J.; Carnevale, J.; Pedley, C.; Blanco, A.; Chan, S.; Collisson, E.A.; Tempero, M.A.; Ko, A.H. Referral Frequency, Attrition Rate, and Outcomes of Germline Testing in Patients with Pancreatic Adenocarcinoma. Fam. Cancer 2019, 18, 241–251. [Google Scholar] [CrossRef]
- Zimmermann, M.T.; Mathison, A.J.; Stodola, T.; Evans, D.B.; Abrudan, J.L.; Demos, W.; Tschannen, M.; Aldakkak, M.; Geurts, J.; Lomberk, G.; et al. Interpreting Sequence Variation in PDAC-Predisposing Genes Using a Multi-Tier Annotation Approach Performed at the Gene, Patient, and Cohort Level. Front. Oncol. 2021, 11, 606820. [Google Scholar] [CrossRef]
- Ryu, K.H.; Park, S.; Chun, J.W.; Cho, E.; Choi, J.; Lee, D.-E.; Shim, H.; Kim, Y.-H.; Han, S.-S.; Park, S.-J.; et al. Prevalence and Risk Factors of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma. Cancer Res. Treat. 2023, 55, 1303–1312. [Google Scholar] [CrossRef] [PubMed]
- Shui, L.; Li, X.; Peng, Y.; Tian, J.; Li, S.; He, D.; Li, A.; Tian, B.; Li, M.; Gao, H.; et al. The Germline/Somatic DNA Damage Repair Gene Mutations Modulate the Therapeutic Response in Chinese Patients with Advanced Pancreatic Ductal Adenocarcinoma. J. Transl. Med. 2021, 19, 301. [Google Scholar] [CrossRef] [PubMed]
- Dudley, B.; Karloski, E.; Monzon, F.A.; Singhi, A.D.; Lincoln, S.E.; Bahary, N.; Brand, R.E. Germline Mutation Prevalence in Individuals with Pancreatic Cancer and a History of Previous Malignancy. Cancer 2018, 124, 1691–1700. [Google Scholar] [CrossRef] [PubMed]
- Jiang, H.; Huang, F.; Chen, X.; Zhang, L.; Shen, M.; Pan, B.; Wang, B.; Guo, W. Germline Mutations in Homologous Recombination Repair Genes among Chinese Pancreatic Ductal Adenocarcinoma Patients Detected Using Next-Generation Sequencing. Molec. Genet. Gen. Med. 2023, 11, e2170. [Google Scholar] [CrossRef]
- Schwartz, M.; Korenbaum, C.; Benfoda, M.; Mary, M.; Colas, C.; Coulet, F.; Parrin, M.; Jonveaux, P.; Ingster, O.; Granier, S.; et al. Familial Pancreatic Adenocarcinoma: A Retrospective Analysis of Germline Genetic Testing in a French Multicentre Cohort. Clin. Genet. 2019, 96, 579–584. [Google Scholar] [CrossRef]
- Walker, E.J.; Goldberg, D.; Gordon, K.M.; Pedley, C.; Carnevale, J.; Cinar, P.; Collisson, E.A.; Tempero, M.A.; Ko, A.H.; Blanco, A.M.; et al. Implementation of an Embedded In-Clinic Genetic Testing Station to Optimize Germline Testing for Patients with Pancreatic Adenocarcinoma. Oncology 2021, 26, e1982–e1991. [Google Scholar] [CrossRef]
- Brand, R.; Borazanci, E.; Speare, V.; Dudley, B.; Karloski, E.; Peters, M.L.B.; Stobie, L.; Bahary, N.; Zeh, H.; Zureikat, A.; et al. Prospective Study of Germline Genetic Testing in Incident Cases of Pancreatic Adenocarcinoma. Cancer 2018, 124, 3520–3527. [Google Scholar] [CrossRef]
- Grant, R.C.; Al-Sukhni, W.; Borgida, A.E.; Holter, S.; Kanji, Z.S.; McPherson, T.; Whelan, E.; Serra, S.; Trinh, Q.M.; Peltekova, V.; et al. Exome Sequencing Identifies Nonsegregating Nonsense ATM and PALB2variants in Familial Pancreatic Cancer. Hum. Genom. 2013, 7, 11. [Google Scholar] [CrossRef]
- Grant, R.C.; Selander, I.; Connor, A.A.; Selvarajah, S.; Borgida, A.; Briollais, L.; Petersen, G.M.; Lerner-Ellis, J.; Holter, S.; Gallinger, S. Prevalence of Germline Mutations in Cancer Predisposition Genes in Patients with Pancreatic Cancer. Gastroenterology 2015, 148, 556–564. [Google Scholar] [CrossRef]
- Roberts, N.J.; Norris, A.L.; Petersen, G.M.; Bondy, M.L.; Brand, R.; Gallinger, S.; Kurtz, R.C.; Olson, S.H.; Rustgi, A.K.; Schwartz, A.G.; et al. Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer. Cancer Discov. 2016, 6, 166–175. [Google Scholar] [CrossRef]
- Zhan, Q.; Wen, C.; Zhao, Y.; Fang, L.; Jin, Y.; Zhang, Z.; Zou, S.; Li, F.; Yang, Y.; Wu, L.; et al. Identification of Copy Number Variation-Driven Molecular Subtypes Informative for Prognosis and Treatment in Pancreatic Adenocarcinoma of a Chinese Cohort. eBioMedicine 2021, 74, 103716. [Google Scholar] [CrossRef] [PubMed]
- Tavano, F.; Gioffreda, D.; Fontana, A.; Palmieri, O.; Gentile, A.; Latiano, T.; Latiano, A.; Latiano, T.P.; Scaramuzzi, M.; Maiello, E.; et al. Evaluation of Inherited Germline Mutations in Cancer Susceptibility Genes among Pancreatic Cancer Patients: A Single-Center Study. Mol. Med. 2023, 29, 14. [Google Scholar] [CrossRef] [PubMed]
- Aguirre, A.J.; Nowak, J.A.; Camarda, N.D.; Moffitt, R.A.; Ghazani, A.A.; Hazar-Rethinam, M.; Raghavan, S.; Kim, J.; Brais, L.K.; Ragon, D.; et al. Real-Time Genomic Characterization of Advanced Pancreatic Cancer to Enable Precision Medicine. Cancer Discov. 2018, 8, 1096–1111. [Google Scholar] [CrossRef] [PubMed]
- Yurgelun, M.B.; Chittenden, A.B.; Morales-Oyarvide, V.; Rubinson, D.A.; Dunne, R.F.; Kozak, M.M.; Qian, Z.R.; Welch, M.W.; Brais, L.K.; Da Silva, A.; et al. Germline Cancer Susceptibility Gene Variants, Somatic Second Hits, and Survival Outcomes in Patients with Resected Pancreatic Cancer. Genet. Med. 2019, 21, 213–223. [Google Scholar] [CrossRef] [PubMed]
- Borazanci, E.; Korn, R.; Liang, W.S.; Guarnieri, C.; Haag, S.; Snyder, C.; Hendrickson, K.; Caldwell, L.; Von Hoff, D.; Jameson, G. An Analysis of Patients with DNA Repair Pathway Mutations Treated with a PARP Inhibitor. Oncology 2020, 25, e60–e67. [Google Scholar] [CrossRef] [PubMed]
- Wong, W.; Lowery, M.A.; Berger, M.F.; Kemel, Y.; Taylor, B.; Zehir, A.; Srinivasan, P.; Bandlamudi, C.; Chou, J.; Capanu, M.; et al. Ampullary Cancer: Evaluation of Somatic and Germline Genetic Alterations and Association with Clinical Outcomes. Cancer 2019, 125, 1441–1448. [Google Scholar] [CrossRef] [PubMed]
- Connor, A.A.; Denroche, R.E.; Jang, G.H.; Timms, L.; Kalimuthu, S.N.; Selander, I.; McPherson, T.; Wilson, G.W.; Chan-Seng-Yue, M.A.; Borozan, I.; et al. Association of Distinct Mutational Signatures with Correlates of Increased Immune Activity in Pancreatic Ductal Adenocarcinoma. JAMA Oncol. 2017, 3, 774. [Google Scholar] [CrossRef] [PubMed]
- Lovecek, M.; Janatova, M.; Skalicky, P.; Zemanek, T.; Havlik, R.; Ehrmann, J.; Strouhal, O.; Zemankova, P.; Lhotova, K.; Borecka, M.; et al. Genetic Analysis of Subsequent Second Primary Malignant Neoplasms in Long-Term Pancreatic Cancer Survivors Suggests New Potential Hereditary Genetic Alterations. CMAR 2019, 11, 599–609. [Google Scholar] [CrossRef]
- Yang, X.R.; Rotunno, M.; Xiao, Y.; Ingvar, C.; Helgadottir, H.; Pastorino, L.; Van Doorn, R.; Bennett, H.; Graham, C.; Sampson, J.N.; et al. Multiple Rare Variants in High-Risk Pancreatic Cancer-Related Genes May Increase Risk for Pancreatic Cancer in a Subset of Patients with and without Germline CDKN2A Mutations. Hum. Genet. 2016, 135, 1241–1249. [Google Scholar] [CrossRef]
- He, Y.; Huang, W.; Tang, Y.; Li, Y.; Peng, X.; Li, J.; Wu, J.; You, N.; Li, L.; Liu, C.; et al. Clinical and Genetic Characteristics in Pancreatic Cancer from Chinese Patients Revealed by Whole Exome Sequencing. Front. Oncol. 2023, 13, 1167144. [Google Scholar] [CrossRef]
- Slater, E.P.; Wilke, L.M.; Böhm, L.B.; Strauch, K.; Lutz, M.; Gercke, N.; Matthäi, E.; Hemminki, K.; Försti, A.; Schlesner, M.; et al. Combinations of Low-Frequency Genetic Variants Might Predispose to Familial Pancreatic Cancer. JPM 2021, 11, 631. [Google Scholar] [CrossRef] [PubMed]
- Uson, P.L.S.; Samadder, N.J.; Riegert-Johnson, D.; Boardman, L.; Borad, M.J.; Ahn, D.; Sonbol, M.B.; Faigel, D.O.; Fukami, N.; Pannala, R.; et al. Clinical Impact of Pathogenic Germline Variants in Pancreatic Cancer: Results from a Multicenter, Prospective, Universal Genetic Testing Study. Clin. Transl. Gastroenterol. 2021, 12, e00414. [Google Scholar] [CrossRef] [PubMed]
- Llach, J.; Moreno, L.; Sánchez, A.; Herrera-Pariente, C.; Ocaña, T.; Cuatrecasas, M.; Rivero-Sánchez, L.; Moreira, R.; Díaz, M.; Jung, G.; et al. Genetic Counseling for Hereditary Gastric and Pancreatic Cancer in High-Risk Gastrointestinal Cancer Clinics: An Effective Strategy. Cancers 2020, 12, 2386. [Google Scholar] [CrossRef] [PubMed]
- Johns, A.L.; McKay, S.H.; Humphris, J.L.; Pinese, M.; Chantrill, L.A.; Mead, R.S.; Tucker, K.; Andrews, L.; Goodwin, A.; Leonard, C.; et al. Lost in Translation: Returning Germline Genetic Results in Genome-Scale Cancer Research. Genome Med. 2017, 9, 41. [Google Scholar] [CrossRef]
- Mandelker, D.; Marra, A.; Zheng-Lin, B.; Selenica, P.; Blanco-Heredia, J.; Zhu, Y.; Gazzo, A.; Wong, D.; Yelskaya, Z.; Rai, V.; et al. Genomic Profiling Reveals Germline Predisposition and Homologous Recombination Deficiency in Pancreatic Acinar Cell Carcinoma. JCO 2023, 41, JCO2300561. [Google Scholar] [CrossRef] [PubMed]
- Chung, A.-K.; Lin, R.-T.; Yeh, C.-C.; Yang, C.-Y.; Wu, C.-J.; Chen, P.-L.; Lin, J.-T. Diagnostic Rate of Germline Pathogenic Variants in Pancreatic Ductal Adenocarcinoma Patients Using Whole Genome Sequencing. Front. Genet. 2023, 14, 1172365. [Google Scholar] [CrossRef] [PubMed]
- Roberts, N.J.; Jiao, Y.; Yu, J.; Kopelovich, L.; Petersen, G.M.; Bondy, M.L.; Gallinger, S.; Schwartz, A.G.; Syngal, S.; Cote, M.L.; et al. ATM Mutations in Patients with Hereditary Pancreatic Cancer. Cancer Discov. 2012, 2, 41–46. [Google Scholar] [CrossRef] [PubMed]
- Xie, F.; Ding, D.; Lin, C.; Cunningham, D.; Wright, M.; Javed, A.A.; Azad, N.; Lee, V.; Donehower, R.; De Jesus-Acosta, A.; et al. RAD51B Harbors Germline Mutations Associated with Pancreatic Ductal Adenocarcinoma. JCO Precis. Oncol. 2022, 6, e2100404. [Google Scholar] [CrossRef]
- Martino, C.; Pandya, D.; Lee, R.; Levy, G.; Lo, T.; Lobo, S.; Frank, R.C. ATM-Mutated Pancreatic Cancer: Clinical and Molecular Response to Gemcitabine/Nab-Paclitaxel After Genome-Based Therapy Resistance. Pancreas 2020, 49, 143–147. [Google Scholar] [CrossRef]
- Mandelker, D.; Zhang, L.; Kemel, Y.; Stadler, Z.K.; Joseph, V.; Zehir, A.; Pradhan, N.; Arnold, A.; Walsh, M.F.; Li, Y.; et al. Mutation Detection in Patients with Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. JAMA 2017, 318, 825. [Google Scholar] [CrossRef]
- Golan, T.; Kindler, H.L.; Park, J.O.; Reni, M.; Macarulla, T.; Hammel, P.; Van Cutsem, E.; Arnold, D.; Hochhauser, D.; McGuinness, D.; et al. Geographic and Ethnic Heterogeneity of Germline BRCA1 or BRCA2 Mutation Prevalence Among Patients with Metastatic Pancreatic Cancer Screened for Entry Into the POLO Trial. JCO 2020, 38, 1442–1454. [Google Scholar] [CrossRef] [PubMed]
- Zheng-Lin, B.; Rainone, M.; Varghese, A.M.; Yu, K.H.; Park, W.; Berger, M.; Mehine, M.; Chou, J.; Capanu, M.; Mandelker, D.; et al. Methylation Analyses Reveal Promoter Hypermethylation as a Rare Cause of “Second Hit” in Germline BRCA1-Associated Pancreatic Ductal Adenocarcinoma. Mol. Diagn. Ther. 2022, 26, 645–653. [Google Scholar] [CrossRef] [PubMed]
- Ozer, M.; Ranganathan, M.; Lecomte, N.; Schvartzman, J.M.; Walch, H.S.; Chatila, W.K.; Hong, J.; Carlo, M.I.; Walsh, M.F.; Sheehan, M.; et al. Concurrent Germline BRCA1/2 and Mismatch Repair Mutations in Young-Onset Pancreatic and Colorectal Cancer: The Importance of Comprehensive Germline and Somatic Characterization to Inform Therapeutic Options. JCO Precis. Oncol. 2022, 6, e2100560. [Google Scholar] [CrossRef] [PubMed]
- Zhen, D.B.; Rabe, K.G.; Gallinger, S.; Syngal, S.; Schwartz, A.G.; Goggins, M.G.; Hruban, R.H.; Cote, M.L.; McWilliams, R.R.; Roberts, N.J.; et al. BRCA1, BRCA2, PALB2, and CDKN2A Mutations in Familial Pancreatic Cancer: A PACGENE Study. Genet. Med. 2015, 17, 569–577. [Google Scholar] [CrossRef] [PubMed]
- Lowery, M.A.; Kelsen, D.P.; Stadler, Z.K.; Yu, K.H.; Janjigian, Y.Y.; Ludwig, E.; D’Adamo, D.R.; Salo-Mullen, E.; Robson, M.E.; Allen, P.J.; et al. An Emerging Entity: Pancreatic Adenocarcinoma Associated with a Known BRCA Mutation: Clinical Descriptors, Treatment Implications, and Future Directions. Oncology 2011, 16, 1397–1402. [Google Scholar] [CrossRef]
- Golan, T.; Stossel, C.; Atias, D.; Buzhor, E.; Halperin, S.; Cohen, K.; Raitses-Gurevich, M.; Glick, Y.; Raskin, S.; Yehuda, D.; et al. Recapitulating the Clinical Scenario of BRCA-associated Pancreatic Cancer in Pre-Clinical Models. Intl. J. Cancer 2018, 143, 179–183. [Google Scholar] [CrossRef] [PubMed]
- Lucas, A.L.; Frado, L.E.; Hwang, C.; Kumar, S.; Khanna, L.G.; Levinson, E.J.; Chabot, J.A.; Chung, W.K.; Frucht, H. BRCA1 and BRCA2 Germline Mutations Are Frequently Demonstrated in Both High-Risk Pancreatic Cancer Screening and Pancreatic Cancer Cohorts. Cancer 2014, 120, 1960–1967. [Google Scholar] [CrossRef] [PubMed]
- Ferrone, C.R.; Levine, D.A.; Tang, L.H.; Allen, P.J.; Jarnagin, W.; Brennan, M.F.; Offit, K.; Robson, M.E. BRCA Germline Mutations in Jewish Patients with Pancreatic Adenocarcinoma. JCO 2009, 27, 433–438. [Google Scholar] [CrossRef]
- Salo-Mullen, E.E.; O’Reilly, E.M.; Kelsen, D.P.; Ashraf, A.M.; Lowery, M.A.; Yu, K.H.; Reidy, D.L.; Epstein, A.S.; Lincoln, A.; Saldia, A.; et al. Identification of Germline Genetic Mutations in Patients with Pancreatic Cancer. Cancer 2015, 121, 4382–4388. [Google Scholar] [CrossRef]
- O’Reilly, E.M.; Lee, J.W.; Lowery, M.A.; Capanu, M.; Stadler, Z.K.; Moore, M.J.; Dhani, N.; Kindler, H.L.; Estrella, H.; Maynard, H.; et al. Phase 1 Trial Evaluating Cisplatin, Gemcitabine, and Veliparib in 2 Patient Cohorts: Germline BRCA Mutation Carriers and Wild-type BRCA Pancreatic Ductal Adenocarcinoma. Cancer 2018, 124, 1374–1382. [Google Scholar] [CrossRef]
- Golan, T.; Sella, T.; O’Reilly, E.M.; Katz, M.H.; Epelbaum, R.; Kelsen, D.P.; Borgida, A.; Maynard, H.; Kindler, H.; Friedmen, E.; et al. Overall survival and clinical characteristics of BRCA mutation carriers with stage I/II pancreatic cancer. Br. J. Cancer 2017, 116, 697–702. [Google Scholar] [CrossRef] [PubMed]
- Dagan, E. Predominant Ashkenazi BRCA1/2 Mutations in Families with Pancreatic Cancer. Genet. Test. 2008, 12, 267–271. [Google Scholar] [CrossRef] [PubMed]
- Lucas, A.L.; Shakya, R.; Lipsyc, M.D.; Mitchel, E.B.; Kumar, S.; Hwang, C.; Deng, L.; Devoe, C.; Chabot, J.A.; Szabolcs, M.; et al. High Prevalence of BRCA1 and BRCA2 Germline Mutations with Loss of Heterozygosity in a Series of Resected Pancreatic Adenocarcinoma and Other Neoplastic Lesions. Clin. Cancer Res. 2013, 19, 3396–3403. [Google Scholar] [CrossRef] [PubMed]
- Fam, H. Delineating the Effects BRCA1 and BRCA2 Loss of Heterozygosity in Pancreatic Cancer Progression. Clin. Genet. 2014, 85, 18–20. [Google Scholar] [CrossRef] [PubMed]
- Golan, T.; Kanji, Z.S.; Epelbaum, R.; Devaud, N.; Dagan, E.; Holter, S.; Aderka, D.; Paluch-Shimon, S.; Kaufman, B.; Gershoni-Baruch, R.; et al. Overall Survival and Clinical Characteristics of Pancreatic Cancer in BRCA Mutation Carriers. Br. J. Cancer 2014, 111, 1132–1138. [Google Scholar] [CrossRef] [PubMed]
- Lener, M.R.; Scott, R.J.; Kluźniak, W.; Baszuk, P.; Cybulski, C.; Wiechowska-Kozłowska, A.; Huzarski, T.; Byrski, T.; Kładny, J.; Pietrzak, S.; et al. Do Founder Mutations Characteristic of Some Cancer Sites Also Predispose to Pancreatic Cancer?: Do Founder Mutations Predispose to Pancreatic Cancer? Int. J. Cancer 2016, 139, 601–606. [Google Scholar] [CrossRef] [PubMed]
- Holter, S.; Borgida, A.; Dodd, A.; Grant, R.; Semotiuk, K.; Hedley, D.; Dhani, N.; Narod, S.; Akbari, M.; Moore, M.; et al. Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients with Pancreatic Adenocarcinoma. JCO 2015, 33, 3124–3129. [Google Scholar] [CrossRef] [PubMed]
- Alimirzaie, S.; Mohamadkhani, A.; Masoudi, S.; Sellars, E.; Boffetta, P.; Malekzadeh, R.; Akbari, M.R.; Pourshams, A. Mutations in Known and Novel Cancer Susceptibility Genes in Young Patients with Pancreatic Cancer. Arch. Iran Med. 2018, 21, 228–233. [Google Scholar]
- Ghiorzo, P.; Pensotti, V.; Fornarini, G.; Sciallero, S.; Battistuzzi, L.; Belli, F.; Bonelli, L.; Borgonovo, G.; Bruno, W.; Gozza, A.; et al. Contribution of Germline Mutations in the BRCA and PALB2 Genes to Pancreatic Cancer in Italy. Fam. Cancer 2012, 11, 41–47. [Google Scholar] [CrossRef]
- Park, J.H.; Jo, J.H.; Jang, S.I.; Chung, M.J.; Park, J.Y.; Bang, S.; Park, S.W.; Song, S.Y.; Lee, H.S.; Cho, J.H. BRCA 1/2 Germline Mutation Predicts the Treatment Response of FOLFIRINOX with Pancreatic Ductal Adenocarcinoma in Korean Patients. Cancers 2022, 14, 236. [Google Scholar] [CrossRef]
- Al-Sukhni, W.; Rothenmund, H.; Eppel Borgida, A.; Zogopoulos, G.; O’Shea, A.-M.; Pollett, A.; Gallinger, S. Germline BRCA1 Mutations Predispose to Pancreatic Adenocarcinoma. Hum. Genet. 2008, 124, 271–278. [Google Scholar] [CrossRef] [PubMed]
- Saha, G.; Singh, R.; Mandal, A.; Das, S.; Chattopadhyay, E.; Panja, P.; Roy, P.; DeSarkar, N.; Gulati, S.; Ghatak, S.; et al. A Novel Hotspot and Rare Somatic Mutation p.A138V, at TP53 Is Associated with Poor Survival of Pancreatic Ductal and Periampullary Adenocarcinoma Patients. Mol. Med. 2020, 26, 59. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Golesworthy, B.; Cuggia, A.; Domecq, C.; Chaudhury, P.; Barkun, J.; Metrakos, P.; Asselah, J.; Bouganim, N.; Gao, Z.-H.; et al. Oncology Clinic-Based Germline Genetic Testing for Exocrine Pancreatic Cancer Enables Timely Return of Results and Unveils Low Uptake of Cascade Testing. J. Med. Genet. 2022, 59, 793–800. [Google Scholar] [CrossRef] [PubMed]
- Vietri, M.T.; D’Elia, G.; Caliendo, G.; Albanese, L.; Signoriello, G.; Napoli, C.; Molinari, A.M. Pancreatic Cancer with Mutation in BRCA1/2, MLH1, and APC Genes: Phenotype Correlation and Detection of a Novel Germline BRCA2 Mutation. Genes 2022, 13, 321. [Google Scholar] [CrossRef] [PubMed]
- Lundy, J.; McKay, O.; Croagh, D.; Ganju, V. Exceptional Response to Olaparib and Pembrolizumab for Pancreatic Adenocarcinoma with Germline BRCA1 Mutation and High Tumor Mutation Burden: Case Report and Literature Review. JCO Precis. Oncol. 2022, 6, e2100437. [Google Scholar] [CrossRef]
- Lal, G.; Liu, G.; Schmocker, B.; Kaurah, P.; Ozcelik, H.; Narod, S.A.; Redston, M.; Gallinger, S. Inherited Predisposition to Pancreatic Adenocarcinoma: Role of Family History and Germ-Line P16, BRCA1, and BRCA2 Mutations. Cancer Res. 2000, 60, 409–416. [Google Scholar] [PubMed]
- Tibiletti, M.G.; Carnevali, I.; Pensotti, V.; Chiaravalli, A.M.; Facchi, S.; Volorio, S.; Mariette, F.; Mariani, P.; Fortuzzi, S.; Pierotti, M.A.; et al. OncoPan®: An NGS-Based Screening Methodology to Identify Molecular Markers for Therapy and Risk Assessment in Pancreatic Ductal Adenocarcinoma. Biomedicines 2022, 10, 1208. [Google Scholar] [CrossRef] [PubMed]
- Lertwilaiwittaya, P.; Roothumnong, E.; Nakthong, P.; Dungort, P.; Meesamarnpong, C.; Tansa-Nga, W.; Pongsuktavorn, K.; Wiboonthanasarn, S.; Tititumjariya, W.; Thongnoppakhun, W.; et al. Thai Patients Who Fulfilled NCCN Criteria for Breast/Ovarian Cancer Genetic Assessment Demonstrated High Prevalence of Germline Mutations in Cancer Susceptibility Genes: Implication to Asian Population Testing. Breast Cancer Res. Treat. 2021, 188, 237–248. [Google Scholar] [CrossRef]
- Pinto, P.; Peixoto, A.; Santos, C.; Rocha, P.; Pinto, C.; Pinheiro, M.; Leça, L.; Martins, A.T.; Ferreira, V.; Bartosch, C.; et al. Analysis of Founder Mutations in Rare Tumors Associated with Hereditary Breast/Ovarian Cancer Reveals a Novel Association of BRCA2 Mutations with Ampulla of Vater Carcinomas. PLoS ONE 2016, 11, e0161438. [Google Scholar] [CrossRef]
- Palacio, S.; McMurry, H.S.; Ali, R.; Donenberg, T.; Silva-Smith, R.; Wideroff, G.; Sussman, D.A.; Rocha Lima, C.M.S.; Hosein, P.J. DNA Damage Repair Deficiency as a Predictive Biomarker for FOLFIRINOX Efficacy in Metastatic Pancreatic Cancer. J. Gastrointest. Oncol. 2019, 10, 1133–1139. [Google Scholar] [CrossRef]
- Terashima, T.; Morizane, C.; Ushiama, M.; Shiba, S.; Takahashi, H.; Ikeda, M.; Mizuno, N.; Tsuji, K.; Yasui, K.; Azemoto, N.; et al. Germline Variants in Cancer-Predisposing Genes in Pancreatic Cancer Patients with a Family History of Cancer. Jpn. J. Clin. Oncol. 2022, 52, hyac110. [Google Scholar] [CrossRef] [PubMed]
- Lecuelle, J.; Aarnink, A.; Tharin, Z.; Truntzer, C.; Ghiringhelli, F. Using Exome Sequencing to Improve Prediction of FOLFIRINOX First Efficacy for Pancreatic Adenocarcinoma. Cancers 2021, 13, 1851. [Google Scholar] [CrossRef]
- Golan, T.; Barenboim, A.; Lahat, G.; Nachmany, I.; Goykhman, Y.; Shacham-Shmueli, E.; Halpern, N.; Brazowski, E.; Geva, R.; Wolf, I.; et al. Increased Rate of Complete Pathologic Response After Neoadjuvant FOLFIRINOX for BRCA Mutation Carriers with Borderline Resectable Pancreatic Cancer. Ann. Surg. Oncol. 2020, 27, 3963–3970. [Google Scholar] [CrossRef] [PubMed]
- Goehringer, C.; Sutter, C.; Kloor, M.; Gebert, J.; Slater, E.P.; Keller, M.; Treiber, I.; Ganschow, P.; Kadmon, M.; Moog, U. Double Germline Mutations in APC and BRCA2 in an Individual with a Pancreatic Tumor. Fam. Cancer 2017, 16, 303–309. [Google Scholar] [CrossRef] [PubMed]
- Jordan, E.J.; Lowery, M.A.; Basturk, O.; Allen, P.J.; Yu, K.H.; Tabar, V.; Beal, K.; Reidy, D.L.; Yamada, Y.; Janjigian, Y.; et al. Brain Metastases in Pancreatic Ductal Adenocarcinoma: Assessment of Molecular Genotype–Phenotype Features—An Entity With an Increasing Incidence? Clin. Color. Cancer 2018, 17, e315–e321. [Google Scholar] [CrossRef] [PubMed]
- Skoulidis, F.; Cassidy, L.D.; Pisupati, V.; Jonasson, J.G.; Bjarnason, H.; Eyfjord, J.E.; Karreth, F.A.; Lim, M.; Barber, L.M.; Clatworthy, S.A.; et al. Germline Brca2 Heterozygosity Promotes KrasG12D -Driven Carcinogenesis in a Murine Model of Familial Pancreatic Cancer. Cancer Cell 2010, 18, 499–509. [Google Scholar] [CrossRef] [PubMed]
- Sonnenblick, A.; Kadouri, L.; Appelbaum, L.; Peretz, T.; Sagi, M.; Goldberg, Y.; Hubert, A. Complete Remission, in BRCA2 Mutation Carrier with Metastatic Pancreatic Adenocarcinoma, Treated with Cisplatin Based Therapy. Cancer Biol. Ther. 2011, 12, 165–168. [Google Scholar] [CrossRef] [PubMed]
- Li, M.; Mou, Y.; Hou, S.; Cao, D.; Li, A. Response of Germline BRCA2-Mutated Advanced Pancreatic Acinar Cell Carcinoma to Olaparib: A Case Report. Medicine 2018, 97, e13113. [Google Scholar] [CrossRef]
- Chapman, J.S.; Asthana, S.; Cade, L.; Chang, M.T.; Wang, Z.; Zaloudek, C.J.; Ueda, S.; Collisson, E.A.; Taylor, B.S. Clinical Sequencing Contributes to a BRCA -Associated Cancer Rediagnosis That Guides an Effective Therapeutic Course. J. Natl. Compr. Canc. Netw. 2015, 13, 835–845. [Google Scholar] [CrossRef]
- Hata, T.; Mizuma, M.; Motoi, F.; Ishida, M.; Ohtsuka, H.; Nakagawa, K.; Morikawa, T.; Furukawa, T.; Unno, M. Germline DNA Damage Repair Gene Mutations in Pancreatic Cancer Patients with Personal/Family Histories of Pancreas/Breast/Ovarian/Prostate Cancer in a Japanese Population. Ann. Gastroent. Surg. 2021, 5, 853–864. [Google Scholar] [CrossRef]
- Dreikhausen, L.; Schulte, N.; Belle, S.; Weidner, P.; Moersdorf, J.; Reissfelder, C.; Ebert, M.P.; Zhan, T. Pancreatic Acinar Cell Carcinoma with Germline BRCA2 Mutation and Severe Pancreatic Panniculitis: A Case Report. Visc. Med. 2021, 37, 447–450. [Google Scholar] [CrossRef] [PubMed]
- Blair, A.B.; Groot, V.P.; Gemenetzis, G.; Wei, J.; Cameron, J.L.; Weiss, M.J.; Goggins, M.; Wolfgang, C.L.; Yu, J.; He, J. BRCA1/BRCA2 Germline Mutation Carriers and Sporadic Pancreatic Ductal Adenocarcinoma. J. Am. Coll. Surg. 2018, 226, 630–637e1. [Google Scholar] [CrossRef] [PubMed]
- Hahn, S.A.; Greenhalf, B.; Ellis, I.; Sina-Frey, M.; Rieder, H.; Korte, B.; Gerdes, B.; Kress, R.; Ziegler, A.; Raeburn, J.A.; et al. BRCA2 Germline Mutations in Familial Pancreatic Carcinoma. JNCI J. Natl. Cancer Inst. 2003, 95, 214–221. [Google Scholar] [CrossRef] [PubMed]
- Furukawa, T.; Sakamoto, H.; Takeuchi, S.; Ameri, M.; Kuboki, Y.; Yamamoto, T.; Hatori, T.; Yamamoto, M.; Sugiyama, M.; Ohike, N.; et al. Whole Exome Sequencing Reveals Recurrent Mutations in BRCA2 and FAT Genes in Acinar Cell Carcinomas of the Pancreas. Sci. Rep. 2015, 5, 8829. [Google Scholar] [CrossRef] [PubMed]
- Murali, K.; Dwarte, T.M.; Nikfarjam, M.; Tucker, K.M.; Vaughan, R.B.; Efthymiou, M.; Collins, A.; Spigelman, A.D.; Salmon, L.; Johns, A.L.; et al. Significant Detection of New Germline Pathogenic Variants in Australian Pancreatic Cancer Screening Program Participants. Hered. Cancer Clin. Pract. 2021, 19, 33. [Google Scholar] [CrossRef] [PubMed]
- Tao, H.; Liu, S.; Huang, D.; Han, X.; Wu, X.; Shao, Y.W.; Hu, Y. Acquired Multiple Secondary BRCA2 Mutations upon PARPi Resistance in a Metastatic Pancreatic Cancer Patient Harboring a BRCA2 Germline Mutation. Am. J. Transl. Res. 2020, 12, 612–617. [Google Scholar]
- Castro, M.; Vierkoetter, K.; Prager, D.; Montgomery, S.; Sedgwick, K. Synchronous Onset of Breast and Pancreatic Cancers: Results of Germline and Somatic Genetic Analysis. Case Rep. Oncol. 2016, 9, 387–394. [Google Scholar] [CrossRef]
- Wang, H.; Mao, C.; Li, N.; Sun, L.; Zheng, Y.; Xu, N. A Case Report of a Dramatic Response to Olaparib in a Patient with Metastatic Pancreatic Cancer Harboring a Germline BRCA2 Mutation. Medicine 2019, 98, e17443. [Google Scholar] [CrossRef]
- Ozçelik, H.; Schmocker, B.; Di Nicola, N.; Shi, X.H.; Langer, B.; Moore, M.; Taylor, B.R.; Narod, S.A.; Darlington, G.; Andrulis, I.L.; et al. Germline BRCA2 6174delT Mutations in Ashkenazi Jewish Pancreatic Cancer Patients. Nat. Genet. 1997, 16, 17–18. [Google Scholar] [CrossRef]
- Figer, A.; Irmin, L.; Geva, R.; Flex, D.; Sulkes, J.; Sulkes, A.; Friedman, E. The Rate of the 6174delT Founder Jewish Mutation in BRCA2 in Patients with Non-Colonic Gastrointestinal Tract Tumours in Israel. Br. J. Cancer 2001, 84, 478–481. [Google Scholar] [CrossRef]
- Murphy, K.M.; Brune, K.A.; Griffin, C.; Sollenberger, J.E.; Petersen, G.M.; Bansal, R.; Hruban, R.H.; Kern, S.E. Evaluation of Candidate Genes MAP2K4, MADH4, ACVR1B, and BRCA2 in Familial Pancreatic Cancer: Deleterious BRCA2 Mutations in 17%. Cancer Res. 2002, 62, 3789–3793. [Google Scholar] [PubMed]
- Takeuchi, S.; Doi, M.; Ikari, N.; Yamamoto, M.; Furukawa, T. Mutations in BRCA1, BRCA2, and PALB2, and a Panel of 50 Cancer-Associated Genes in Pancreatic Ductal Adenocarcinoma. Sci. Rep. 2018, 8, 8105. [Google Scholar] [CrossRef]
- Pishvaian, M.J.; Biankin, A.V.; Bailey, P.; Chang, D.K.; Laheru, D.; Wolfgang, C.L.; Brody, J.R. BRCA2 Secondary Mutation-Mediated Resistance to Platinum and PARP Inhibitor-Based Therapy in Pancreatic Cancer. Br. J. Cancer 2017, 116, 1021–1026. [Google Scholar] [CrossRef] [PubMed]
- White, K.; Held, K.R.; Weber, B.H.F. A BRCA2 Germ-Line Mutation in Familial Pancreatic Carcinoma. Int. J. Cancer 2001, 91, 742–744. [Google Scholar] [CrossRef] [PubMed]
- Sharma, M.B.; Carus, A.; Sunde, L.; Hamilton-Dutoit, S.; Ladekarl, M. BRCA-Associated Pancreatico-Biliary Neoplasms: Four Cases Illustrating the Emerging Clinical Impact of Genotyping. Acta Oncol. 2016, 55, 377–381. [Google Scholar] [CrossRef] [PubMed]
- Lee, K.; Yoo, C.; Kim, K.; Park, K.-J.; Chang, H.-M.; Kim, T.W.; Lee, J.-L.; Lee, W.; Lee, S.S.; Park, D.H.; et al. Germline BRCA Mutations in Asian Patients with Pancreatic Adenocarcinoma: A Prospective Study Evaluating Risk Category for Genetic Testing. Investig. New Drugs 2018, 36, 163–169. [Google Scholar] [CrossRef]
- Schultheis, A.M.; Nguyen, G.P.; Ortmann, M.; Kruis, W.; Büttner, R.; Schildhaus, H.-U.; Markiefka, B. Squamous Cell Carcinoma of the Pancreas in a Patient with Germline BRCA2 Mutation-Response to Neoadjuvant Radiochemotherapy. Case Rep. Oncol. Med. 2014, 2014, 860532. [Google Scholar] [CrossRef]
- Kryklyva, V.; Haj Mohammad, N.; Morsink, F.H.M.; Ligtenberg, M.J.L.; Offerhaus, G.J.A.; Nagtegaal, I.D.; De Leng, W.W.J.; Brosens, L.A.A. Pancreatic Acinar Cell Carcinoma Is Associated with BRCA2 Germline Mutations: A Case Report and Literature Review. Cancer Biol. Ther. 2019, 20, 949–955. [Google Scholar] [CrossRef]
- Shimmura, H.; Kuramochi, H.; Jibiki, N.; Katagiri, S.; Nishino, T.; Araida, T. Dramatic Response of FOLFIRINOX Regimen in a Collision Pancreatic Adenocarcinoma Patient with a Germline BRCA2 Mutation: A Case Report. Jpn. J. Clin. Oncol. 2019, 49, 1049–1054. [Google Scholar] [CrossRef]
- Bruno, W.; Andreotti, V.; Bisio, A.; Pastorino, L.; Fornarini, G.; Sciallero, S.; Bianchi-Scarrà, G.; Inga, A.; Ghiorzo, P. Functional Analysis of a CDKN2A 5’UTR Germline Variant Associated with Pancreatic Cancer Development. PLoS ONE 2017, 12, e0189123. [Google Scholar] [CrossRef]
- Ghiorzo, P.; Fornarini, G.; Sciallero, S.; Battistuzzi, L.; Belli, F.; Bernard, L.; Bonelli, L.; Borgonovo, G.; Bruno, W.; De Cian, F.; et al. CDKN2A Is the Main Susceptibility Gene in Italian Pancreatic Cancer Families. J. Med. Genet. 2012, 49, 164–170. [Google Scholar] [CrossRef]
- Maker, A.V.; Warth, J.A.; Zinner, M.J. Novel Presentation of a Familial Pancreatic Cancer Syndrome. J. Gastrointest. Surg. 2009, 13, 1151–1154. [Google Scholar] [CrossRef]
- Bottillo, I.; Valiante, M.; Menale, L.; Paiardini, A.; Papi, L.; Janson, G.; Sestini, R.; Iorio, A.; De Simone, P.; Frascione, P.; et al. A Novel CDKN2A In-Frame Deletion Associated with Pancreatic Cancer-Melanoma Syndrome. Dermatol. Online J. 2020, 15, 26. [Google Scholar] [CrossRef]
- Pissa, M.; Helkkula, T.; Appelqvist, F.; Silander, G.; Borg, Å.; Pettersson, J.; Lapins, J.; Nielsen, K.; Höiom, V.; Helgadottir, H. CDKN2A Genetic Testing in Melanoma-Prone Families in Sweden in the Years 2015–2020: Implications for Novel National Recommendations. Acta Oncol. 2021, 60, 888–896. [Google Scholar] [CrossRef]
- Ghiorzo, P.; Gargiulo, S.; Nasti, S.; Pastorino, L.; Battistuzzi, L.; Bruno, W.; Bonelli, L.; Taveggia, P.; Pugliese, V.; Borgonovo, G.; et al. Predicting the Risk of Pancreatic Cancer: On CDKN2A Mutations in the Melanoma-Pancreatic Cancer Syndrome in Italy. JCO 2007, 25, 5336–5337. [Google Scholar] [CrossRef]
- Moore, P.S.; Zamboni, G.; Falconi, M.; Bassi, C.; Scarpa, A. A Novel Germline Mutation, P48T, in theCDKN2A/P16 Gene in a Patient with Pancreatic Carcinoma. Hum. Mutat. 2000, 16, 447–448. [Google Scholar] [CrossRef]
- Dębniak, T.; Van De Wetering, T.; Scott, R.; Nagay, L.; Cybulski, C.; Górski, B.; Jakubowska, A.; Gronwald, J.; Masojć, B.; Huzarski, T.; et al. Low Prevalence of CDKN2A/ARF Mutations among Early-Onset Cancers of Breast, Pancreas and Malignant Melanoma in Poland. Eur. J. Cancer Prev. 2008, 17, 389–391. [Google Scholar] [CrossRef]
- Lal, G.; Liu, L.; Hogg, D.; Lassam, N.J.; Redston, M.S.; Gallinger, S. Patients with Both Pancreatic Adenocarcinoma and Melanoma May Harbor Germline CDKN2A Mutations. Genes Chromosomes Cancer 2000, 27, 358–361. [Google Scholar] [CrossRef]
- Bartsch, D.K.; Sina-Frey, M.; Lang, S.; Wild, A.; Gerdes, B.; Barth, P.; Kress, R.; Grützmann, R.; Colombo-Benkmann, M.; Ziegler, A.; et al. CDKN2A Germline Mutations in Familial Pancreatic Cancer. Ann. Surg. 2002, 236, 730–737. [Google Scholar] [CrossRef]
- Lee, C.L.; Holter, S.; Borgida, A.; Dodd, A.; Ramotar, S.; Grant, R.; Wasson, K.; Elimova, E.; Jang, R.W.; Moore, M.; et al. Germline BRCA2 Variants in Advanced Pancreatic Acinar Cell Carcinoma: A Case Report and Review of Literature. World J. Gastroenterol. 2022, 28, 6421–6432. [Google Scholar] [CrossRef]
- Levin, T.; Mæhle, L. Uptake of Genetic Counseling, Genetic Testing and Surveillance in Hereditary Malignant Melanoma (CDKN2A) in Norway. Fam. Cancer 2017, 16, 257–265. [Google Scholar] [CrossRef]
- Soufir, N.; Lacapere, J.J.; Bertrand, G.; Matichard, E.; Meziani, R.; Mirebeau, D.; Descamps, V.; Gérard, B.; Archimbaud, A.; Ollivaud, L.; et al. Germline Mutations of the INK4a-ARF Gene in Patients with Suspected Genetic Predisposition to Melanoma. Br. J. Cancer 2004, 90, 503–509. [Google Scholar] [CrossRef]
- Juan, F.M.D.; Escribano, M.R.; Lapiedra, C.M.; Alcantara, F.M.D.; Soto, M.C.; Fons, A.C.; Machado, I. Pancreatic Adenosquamous Carcinoma and Intraductal Papillary Mucinous Neoplasm in a CDKN2A Germline Mutation Carrier. WJGO 2017, 9, 390. [Google Scholar] [CrossRef]
- Gerdes, B.; Bartsch, D.K.; Ramaswamy, A.; Kersting, M.; Wild, A.; Schuermann, M.; Frey, M.; Rothmund, M. Multiple Primary Tumors as an Indicator for p16INK4a Germline Mutations in Pancreatic Cancer Patients? Pancreas 2000, 21, 369–375. [Google Scholar] [CrossRef]
- Potjer, T.P.; Kranenburg, H.E.; Bergman, W.; De Vos Tot Nederveen Cappel, W.H.; Van Monsjou, H.S.; Barge-Schaapveld, D.Q.C.M.; Vasen, H.F.A. Prospective Risk of Cancer and the Influence of Tobacco Use in Carriers of the P16-Leiden Germline Variant. Eur. J. Hum. Genet. 2015, 23, 711–714. [Google Scholar] [CrossRef]
- Koorstra, J.-B.M.; Maitra, A.; Morsink, F.H.M.; Drillenburg, P.; Ten Kate, F.J.W.; Hruban, R.H.; Offerhaus, J.A. Undifferentiated Carcinoma with Osteoclastic Giant Cells (UCOCGC) of the Pancreas Associated With the Familial Atypical Multiple Mole Melanoma Syndrome (FAMMM). Am. J. Surg. Pathol. 2008, 32, 1905–1909. [Google Scholar] [CrossRef]
- Yang, X.R.; Jessop, L.; Myers, T.; Amundadottir, L.; Pfeiffer, R.M.; Wheeler, W.; Pike, K.M.; Yuenger, J.; Burdett, L.; Yeager, M.; et al. Lack of Germline PALB2 Mutations in Melanoma-Prone Families with CDKN2A Mutations and Pancreatic Cancer. Fam. Cancer 2011, 10, 545–548. [Google Scholar] [CrossRef]
- Goldstein, A.M. Prospective Risk of Cancer in CDKN2A Germline Mutation Carriers. J. Med. Genet. 2004, 41, 421–424. [Google Scholar] [CrossRef]
- McWilliams, R.R.; Wieben, E.D.; Rabe, K.G.; Pedersen, K.S.; Wu, Y.; Sicotte, H.; Petersen, G.M. Prevalence of CDKN2A Mutations in Pancreatic Cancer Patients: Implications for Genetic Counseling. Eur. J. Hum. Genet. 2011, 19, 472–478. [Google Scholar] [CrossRef]
- Ghiorzo, P.; Pastorino, L.; Bonelli, L.; Cusano, R.; Nicora, A.; Zupo, S.; Queirolo, P.; Sertoli, M.; Pugliese, V.; Bianchi-Scarrà, G. INK4/ARF Germline Alterations in Pancreatic Cancer Patients. Ann. Oncol. 2004, 15, 70–78. [Google Scholar] [CrossRef]
- Borg, A.; Sandberg, T.; Nilsson, K.; Johannsson, O.; Klinker, M.; Masback, A.; Westerdahl, J.; Olsson, H.; Ingvar, C. High Frequency of Multiple Melanomas and Breast and Pancreas Carcinomas in CDKN2A Mutation-Positive Melanoma Families. JNCI J. Natl. Cancer Inst. 2000, 92, 1260–1266. [Google Scholar] [CrossRef]
- Llach, J.; Aguilera, P.; Sánchez, A.; Ginès, A.; Fernández-Esparrach, G.; Soy, G.; Sendino, O.; Vaquero, E.; Carballal, S.; Ausania, F.; et al. Pancreatic Cancer Surveillance in Carriers of a Germline Pathogenic Variant in CDKN2A. Cancers 2023, 15, 1690. [Google Scholar] [CrossRef]
- Parker, J.F. Pancreatic Carcinoma Surveillance in Patients with Familial Melanoma. Arch. Dermatol. 2003, 139, 1019. [Google Scholar] [CrossRef]
- Puig, S.; Potrony, M.; Cuellar, F.; Puig-Butille, J.A.; Carrera, C.; Aguilera, P.; Nagore, E.; Garcia-Casado, Z.; Requena, C.; Kumar, R.; et al. Characterization of Individuals at High Risk of Developing Melanoma in Latin America: Bases for Genetic Counseling in Melanoma. Genet. Med. 2016, 18, 727–736. [Google Scholar] [CrossRef]
- Tanyi, M.; Olasz, J.; Lukács, G.; Tanyi, J.L.; Tóth, L.; Antal-Szalmás, P.; Ress, Z.; Bubán, T.; András, C.; Damjanovich, L. A New Mutation in Muir-Torre Syndrome Associated with Familiar Transmission of Different Gastrointestinal Adenocarcinomas. Eur. J. Surg. Oncol. EJSO 2009, 35, 1128–1130. [Google Scholar] [CrossRef]
- Latham, A.; Srinivasan, P.; Kemel, Y.; Shia, J.; Bandlamudi, C.; Mandelker, D.; Middha, S.; Hechtman, J.; Zehir, A.; Dubard-Gault, M.; et al. Microsatellite Instability Is Associated with the Presence of Lynch Syndrome Pan-Cancer. JCO 2019, 37, 286–295. [Google Scholar] [CrossRef]
- Grandval, P.; Barouk-Simonet, E.; Bronner, M.; Buisine, M.-P.; Moretta, J.; Tinat, J.; Olschwang, S. Is the Controversy on Breast Cancer as Part of the Lynch-Related Tumor Spectrum Still Open? Fam. Cancer 2012, 11, 681–683. [Google Scholar] [CrossRef]
- Malgerud, L.; Lindberg, J.; Wirta, V.; Gustafsson-Liljefors, M.; Karimi, M.; Moro, C.F.; Stecker, K.; Picker, A.; Huelsewig, C.; Stein, M.; et al. Bioinformatory-assisted Analysis of Next-generation Sequencing Data for Precision Medicine in Pancreatic Cancer. Mol. Oncol. 2017, 11, 1413–1429. [Google Scholar] [CrossRef]
- Banville, N.; Geraghty, R.; Fox, E.; Leahy, D.; Green, A.; Keegan, D.; Geoghegan, J.; Odonoghue, D.; Hyland, J.; Sheahan, K. Medullary Carcinoma of the Pancreas in a Man with Hereditary Nonpolyposis Colorectal Cancer Due to a Mutation of the MSH2 Mismatch Repair Gene. Hum. Pathol. 2006, 37, 1498–1502. [Google Scholar] [CrossRef]
- Gargiulo, S.; Torrini, M.; Ollila, S.; Nasti, S.; Pastorino, L.; Cusano, R.; Bonelli, L.; Battistuzzi, L.; Mastracci, L.; Bruno, W.; et al. Germline MLH1 and MSH2 Mutations in Italian Pancreatic Cancer Patients with Suspected Lynch Syndrome. Fam. Cancer 2009, 8, 547–553. [Google Scholar] [CrossRef]
- Peng, S.-H.; Chen, B.-B.; Kuo, T.-C.; Lee, J.-C.; Yang, S.-H. Maintenance Therapy of Low-Dose Nivolumab, S-1, and Leucovorin in Metastatic Pancreatic Adenocarcinoma with a Germline Mutation of MSH6: A Case Report. Front. Immunol. 2022, 13, 1077840. [Google Scholar] [CrossRef] [PubMed]
- Ohmoto, A.; Yachida, S.; Kubo, E.; Takai, E.; Suzuki, M.; Shimada, K.; Okusaka, T.; Morizane, C. Clinicopathologic Features and Germline Sequence Variants in Young Patients (≤40 Years Old) with Pancreatic Ductal Adenocarcinoma. Pancreas 2016, 45, 1056–1061. [Google Scholar] [CrossRef] [PubMed]
- Muhammad, N.; Sadaqat, R.; Naeemi, H.; Masood, I.; Hassan, U.; Ijaz, B.; Hanif, F.; Syed, A.A.; Yusuf, M.A.; Rashid, M.U. Contribution of Germline PALB2 Variants to an Unselected and Prospectively Registered Pancreatic Cancer Patient Cohort in Pakistan. HPB 2022, 24, 2134–2144. [Google Scholar] [CrossRef] [PubMed]
- Lener, M.R.; Kashyap, A.; Kluźniak, W.; Cybulski, C.; Soluch, A.; Pietrzak, S.; Huzarski, T.; Gronwald, J.; Lubiński, J. The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome. Cancer Res. Treat. 2017, 49, 430–436. [Google Scholar] [CrossRef] [PubMed]
- Borecka, M.; Zemankova, P.; Vocka, M.; Soucek, P.; Soukupova, J.; Kleiblova, P.; Sevcik, J.; Kleibl, Z.; Janatova, M. Mutation Analysis of the PALB2 Gene in Unselected Pancreatic Cancer Patients in the Czech Republic. Cancer Genet. 2016, 209, 199–204. [Google Scholar] [CrossRef] [PubMed]
- Yang, X.; Leslie, G.; Doroszuk, A.; Schneider, S.; Allen, J.; Decker, B.; Dunning, A.M.; Redman, J.; Scarth, J.; Plaskocinska, I.; et al. Cancer Risks Associated with Germline PALB2 Pathogenic Variants: An International Study of 524 Families. JCO 2020, 38, 674–685. [Google Scholar] [CrossRef] [PubMed]
- Slater, E.; Langer, P.; Niemczyk, E.; Strauch, K.; Butler, J.; Habbe, N.; Neoptolemos, J.; Greenhalf, W.; Bartsch, D. PALB2 Mutations in European Familial Pancreatic Cancer Families. Clin. Genet. 2010, 78, 490–494. [Google Scholar] [CrossRef]
- Peterlongo, P.; Catucci, I.; Pasquini, G.; Verderio, P.; Peissel, B.; Barile, M.; Varesco, L.; Riboni, M.; Fortuzzi, S.; Manoukian, S.; et al. Palb2 Germline Mutations in Familial Breast Cancer Cases with Personal and Family History of Pancreatic Cancer. Breast Cancer Res. Treat. 2011, 126, 825–828. [Google Scholar] [CrossRef]
- Abe, K.; Ueki, A.; Urakawa, Y.; Kitago, M.; Yoshihama, T.; Nanki, Y.; Kitagawa, Y.; Aoki, D.; Kosaki, K.; Hirasawa, A. Familial Pancreatic Cancer with PALB2 and NBN Pathogenic Variants: A Case Report. Hered. Cancer Clin. Pract. 2021, 19, 5. [Google Scholar] [CrossRef]
- Boeck, S.; Mehraein, Y.; Ormanns, S.; Kruger, S.; Westphalen, C.B.; Haas, M.; Jung, A.; Kirchner, T.; Heinemann, V. Mismatch-Repair-Deficient Metastatic Pancreatic Ductal Adenocarcinoma with a Germline PALB2 Mutation: Unusual Genetics, Unusual Clinical Course. Ann. Oncol. 2017, 28, 438–439. [Google Scholar] [CrossRef]
- Jones, S.; Hruban, R.H.; Kamiyama, M.; Borges, M.; Zhang, X.; Parsons, D.W.; Lin, J.C.-H.; Palmisano, E.; Brune, K.; Jaffee, E.M.; et al. Exomic Sequencing Identifies PALB2 as a Pancreatic Cancer Susceptibility Gene. Science 2009, 324, 217. [Google Scholar] [CrossRef] [PubMed]
- Bernstein Molho, R.; Zalmanoviz, S.; Laitman, Y.; Friedman, E. De Novo Pathogenic Germline Variant in PALB2 in a Patient with Pancreatic Cancer. Fam. Cancer 2020, 19, 193–196. [Google Scholar] [CrossRef] [PubMed]
- Hofstatter, E.W.; Domchek, S.M.; Miron, A.; Garber, J.; Wang, M.; Componeschi, K.; Boghossian, L.; Miron, P.L.; Nathanson, K.L.; Tung, N. PALB2 Mutations in Familial Breast and Pancreatic Cancer. Fam. Cancer 2011, 10, 225–231. [Google Scholar] [CrossRef] [PubMed]
- Tischkowitz, M.D.; Sabbaghian, N.; Hamel, N.; Borgida, A.; Rosner, C.; Taherian, N.; Srivastava, A.; Holter, S.; Rothenmund, H.; Ghadirian, P.; et al. Analysis of the Gene Coding for the BRCA2-Interacting Protein PALB2 in Familial and Sporadic Pancreatic Cancer. Gastroenterology 2009, 137, 1183–1186. [Google Scholar] [CrossRef] [PubMed]
- Wang, Y.; Cuggia, A.; Pacis, A.; Boileau, J.-C.; Marcus, V.A.; Gao, Z.-H.; Chong, G.; Foulkes, W.D.; Zogopoulos, G. Pancreatic Cancer Progression in a Patient with Lynch Syndrome Receiving Immunotherapy: A Cautionary Tale. J. Natl. Compr. Cancer Netw. 2021, 19, 883–887. [Google Scholar] [CrossRef]
- Sato, N.; Rosty, C.; Jansen, M.; Fukushima, N.; Ueki, T.; Yeo, C.J.; Cameron, J.L.; Iacobuzio-Donahue, C.A.; Hruban, R.H.; Goggins, M. STK11/LKB1 Peutz-Jeghers Gene Inactivation in Intraductal Papillary-Mucinous Neoplasms of the Pancreas. Am. J. Pathol. 2001, 159, 2017–2022. [Google Scholar] [CrossRef]
- Su, G.H.; Hruban, R.H.; Bansal, R.K.; Bova, G.S.; Tang, D.J.; Shekher, M.C.; Westerman, A.M.; Entius, M.M.; Goggins, M.; Yeo, C.J.; et al. Germline and Somatic Mutations of the STK11/LKB1 Peutz-Jeghers Gene in Pancreatic and Biliary Cancers. Am. J. Pathol. 1999, 154, 1835–1840. [Google Scholar] [CrossRef]
- Resta, N.; Pierannunzio, D.; Lenato, G.M.; Stella, A.; Capocaccia, R.; Bagnulo, R.; Lastella, P.; Susca, F.C.; Bozzao, C.; Loconte, D.C.; et al. Cancer Risk Associated with STK11/LKB1 Germline Mutations in Peutz–Jeghers Syndrome Patients: Results of an Italian Multicenter Study. Dig. Liver Dis. 2013, 45, 606–611. [Google Scholar] [CrossRef]
- Wang, Y.; Cuggia, A.; Chen, Y.-I.; Parent, J.; Stanek, A.; Denroche, R.E.; Zhang, A.; Grant, R.C.; Domecq, C.; Golesworthy, B.; et al. Is Biannual Surveillance for Pancreatic Cancer Sufficient in Individuals with Genetic Syndromes or Familial Pancreatic Cancer? J. Natl. Compr. Cancer Netw. 2022, 20, 663–673.e12. [Google Scholar] [CrossRef]
- Liu, Q.; Wang, Z.; Yu, C.; Zhu, J.; Liu, C.; Li, X.; Ren, L.; Li, T. Intraductal Oncocytic Papillary Neoplasm Arising in Peutz-Jeghers Syndrome Bile Duct: A Unique Case Report. Diagn. Pathol. 2022, 17, 96. [Google Scholar] [CrossRef]
- Ruijs, M.W.G.; Verhoef, S.; Rookus, M.A.; Pruntel, R.; Van Der Hout, A.H.; Hogervorst, F.B.L.; Kluijt, I.; Sijmons, R.H.; Aalfs, C.M.; Wagner, A.; et al. TP53 Germline Mutation Testing in 180 Families Suspected of Li-Fraumeni Syndrome: Mutation Detection Rate and Relative Frequency of Cancers in Different Familial Phenotypes. J. Med. Genet. 2010, 47, 421–428. [Google Scholar] [CrossRef] [PubMed]
- Ide, H.; Terado, Y.; Tokiwa, S.; Nishio, K.; Saito, K.; Isotani, S.; Kamiyama, Y.; Muto, S.; Imamura, T.; Horie, S. Novel Germ Line Mutation P53-P177R in Adult Adrenocortical Carcinoma Producing Neuron-Specific Enolase as a Possible Marker. Jpn. J. Clin. Oncol. 2010, 40, 815–818. [Google Scholar] [CrossRef] [PubMed]
- McWilliams, R.R.; Wieben, E.D.; Chaffee, K.G.; Antwi, S.O.; Raskin, L.; Olopade, O.I.; Li, D.; Highsmith, W.E.; Colon-Otero, G.; Khanna, L.G.; et al. CDKN2A Germline Rare Coding Variants and Risk of Pancreatic Cancer in Minority Populations. Cancer Epidemiol. Biomark. Prev. 2018, 27, 1364–1370. [Google Scholar] [CrossRef] [PubMed]
- Helgadottir, H.; Höiom, V.; Jönsson, G.; Tuominen, R.; Ingvar, C.; Borg, Å.; Olsson, H.; Hansson, J. High Risk of Tobacco-Related Cancers in CDKN2A Mutation-Positive Melanoma Families. J. Med. Genet. 2014, 51, 545–552. [Google Scholar] [CrossRef] [PubMed]
- Paiella, S.; Capurso, G.; Cavestro, G.M.; Butturini, G.; Pezzilli, R.; Salvia, R.; Signoretti, M.; Crippa, S.; Carrara, S.; Frigerio, I.; et al. Results of First-Round of Surveillance in Individuals at High-Risk of Pancreatic Cancer from the AISP (Italian Association for the Study of the Pancreas) Registry. Am. J. Gastroenterol. 2019, 114, 665–670. [Google Scholar] [CrossRef] [PubMed]
- Paiella, S.; Capurso, G.; Carrara, S.; Secchettin, E.; Casciani, F.; Frigerio, I.; Zerbi, A.; Archibugi, L.; Bonifacio, C.; Malleo, G.; et al. Outcomes of a 3-Year Prospective Surveillance in Individuals at High-Risk for Pancreatic Cancer. Am. J. Gastroenterol. 2023, in press. [Google Scholar] [CrossRef] [PubMed]
- Cortesi, L.; Piombino, C.; Toss, A. Germline Mutations in Other Homologous Recombination Repair-Related Genes Than BRCA1/2: Predictive or Prognostic Factors? J. Pers. Med. 2021, 11, 245. [Google Scholar] [CrossRef]
- Venkitaraman, A.R. Cancer Susceptibility and the Functions of BRCA1 and BRCA2. Cell 2002, 108, 171–182. [Google Scholar] [CrossRef]
- Walsh, C.S. Two Decades beyond BRCA1/2: Homologous Recombination, Hereditary Cancer Risk and a Target for Ovarian Cancer Therapy. Gynecol. Oncol. 2015, 137, 343–350. [Google Scholar] [CrossRef]
- Angeli, D.; Salvi, S.; Tedaldi, G. Genetic Predisposition to Breast and Ovarian Cancers: How Many and Which Genes to Test? IJMS 2020, 21, 1128. [Google Scholar] [CrossRef]
- Alvarez, C.; Tapia, T.; Perez-Moreno, E.; Gajardo-Meneses, P.; Ruiz, C.; Rios, M.; Missarelli, C.; Silva, M.; Cruz, A.; Matamala, L.; et al. BRCA1 and BRCA2 Founder Mutations Account for 78% of Germline Carriers among Hereditary Breast Cancer Families in Chile. Oncotarget 2017, 8, 74233–74243. [Google Scholar] [CrossRef] [PubMed]
- ElBiad, O.; Laraqui, A.; El Boukhrissi, F.; Mounjid, C.; Lamsisi, M.; Bajjou, T.; Elannaz, H.; Lahlou, A.I.; Kouach, J.; Benchekroune, K.; et al. Prevalence of Specific and Recurrent/Founder Pathogenic Variants in BRCA Genes in Breast and Ovarian Cancer in North Africa. BMC Cancer 2022, 22, 208. [Google Scholar] [CrossRef] [PubMed]
- Hamel, N.; Feng, B.-J.; Foretova, L.; Stoppa-Lyonnet, D.; Narod, S.A.; Imyanitov, E.; Sinilnikova, O.; Tihomirova, L.; Lubinski, J.; Gronwald, J.; et al. On the Origin and Diffusion of BRCA1 c.5266dupC (5382insC) in European Populations. Eur. J. Hum. Genet. 2011, 19, 300–306. [Google Scholar] [CrossRef] [PubMed]
- McKinnon, P.J. ATM and Ataxia Telangiectasia. EMBO Rep. 2004, 5, 772–776. [Google Scholar] [CrossRef] [PubMed]
- Borja, N.A.; Silva-Smith, R.; Huang, M.; Parekh, D.J.; Sussman, D.; Tekin, M. Atypical ATMs: Broadening the Phenotypic Spectrum of ATM-Associated Hereditary Cancer. Front. Oncol. 2023, 13, 1068110. [Google Scholar] [CrossRef]
- Kim, H.; Saka, B.; Knight, S.; Borges, M.; Childs, E.; Klein, A.; Wolfgang, C.; Herman, J.; Adsay, V.N.; Hruban, R.H.; et al. Having Pancreatic Cancer with Tumoral Loss of ATM and Normal TP53 Protein Expression Is Associated with a Poorer Prognosis. Clin. Cancer Res. 2014, 20, 1865–1872. [Google Scholar] [CrossRef]
- Thompson, D.; Duedal, S.; Kirner, J.; McGuffog, L.; Last, J.; Reiman, A.; Byrd, P.; Taylor, M.; Easton, D.F. Cancer Risks and Mortality in Heterozygous ATM Mutation Carriers. J. Natl. Cancer Inst. 2005, 97, 813–822. [Google Scholar] [CrossRef]
- Tischkowitz, M.; Balmaña, J.; Foulkes, W.D.; James, P.; Ngeow, J.; Schmutzler, R.; Voian, N.; Wick, M.J.; Stewart, D.R.; Pal, T.; et al. Management of Individuals with Germline Variants in PALB2: A Clinical Practice Resource of the American College of Medical Genetics and Genomics (ACMG). Genet. Med. 2021, 23, 1416–1423. [Google Scholar] [CrossRef]
- Wattenberg, M.M.; Asch, D.; Yu, S.; O’Dwyer, P.J.; Domchek, S.M.; Nathanson, K.L.; Rosen, M.A.; Beatty, G.L.; Siegelman, E.S.; Reiss, K.A. Platinum Response Characteristics of Patients with Pancreatic Ductal Adenocarcinoma and a Germline BRCA1, BRCA2 or PALB2 Mutation. Br. J. Cancer 2020, 122, 333–339. [Google Scholar] [CrossRef]
- O’Reilly, E.M.; Lee, J.W.; Zalupski, M.; Capanu, M.; Park, J.; Golan, T.; Tahover, E.; Lowery, M.A.; Chou, J.F.; Sahai, V.; et al. Randomized, Multicenter, Phase II Trial of Gemcitabine and Cisplatin with or without Veliparib in Patients with Pancreas Adenocarcinoma and a Germline BRCA/PALB2 Mutation. J. Clin. Oncol. 2020, 38, 1378–1388. [Google Scholar] [CrossRef]
- Pantaleo, A.; Forte, G.; Cariola, F.; Valentini, A.M.; Fasano, C.; Sanese, P.; Grossi, V.; Buonadonna, A.L.; De Marco, K.; Lepore Signorile, M.; et al. Tumor Testing and Genetic Analysis to Identify Lynch Syndrome Patients in an Italian Colorectal Cancer Cohort. Cancers 2023, 15, 5061. [Google Scholar] [CrossRef]
- Lepore Signorile, M.; Disciglio, V.; Di Carlo, G.; Pisani, A.; Simone, C.; Ingravallo, G. From Genetics to Histomolecular Characterization: An Insight into Colorectal Carcinogenesis in Lynch Syndrome. Int. J. Mol. Sci. 2021, 22, 6767. [Google Scholar] [CrossRef] [PubMed]
- Kastrinos, F.; Mukherjee, B.; Tayob, N.; Wang, F.; Sparr, J.; Raymond, V.M.; Bandipalliam, P.; Stoffel, E.M.; Gruber, S.B.; Syngal, S. Risk of Pancreatic Cancer in Families with Lynch Syndrome. JAMA 2009, 302, 1790–1795. [Google Scholar] [CrossRef] [PubMed]
- Win, A.K.; Young, J.P.; Lindor, N.M.; Tucker, K.M.; Ahnen, D.J.; Young, G.P.; Buchanan, D.D.; Clendenning, M.; Giles, G.G.; Winship, I.; et al. Colorectal and Other Cancer Risks for Carriers and Noncarriers from Families with a DNA Mismatch Repair Gene Mutation: A Prospective Cohort Study. J. Clin. Oncol. 2012, 30, 958–964. [Google Scholar] [CrossRef] [PubMed]
- Betz, B.; Theiss, S.; Aktas, M.; Konermann, C.; Goecke, T.O.; Möslein, G.; Schaal, H.; Royer-Pokora, B. Comparative in Silico Analyses and Experimental Validation of Novel Splice Site and Missense Mutations in the Genes MLH1 and MSH2. J. Cancer Res. Clin. Oncol. 2010, 136, 123–134. [Google Scholar] [CrossRef]
- Tournier, I.; Vezain, M.; Martins, A.; Charbonnier, F.; Baert-Desurmont, S.; Olschwang, S.; Wang, Q.; Buisine, M.P.; Soret, J.; Tazi, J.; et al. A Large Fraction of Unclassified Variants of the Mismatch Repair Genes MLH1 and MSH2 Is Associated with Splicing Defects. Hum. Mutat. 2008, 29, 1412–1424. [Google Scholar] [CrossRef]
- Tricarico, R.; Kasela, M.; Mareni, C.; Thompson, B.A.; Drouet, A.; Staderini, L.; Gorelli, G.; Crucianelli, F.; Ingrosso, V.; Kantelinen, J.; et al. Assessment of the InSiGHT Interpretation Criteria for the Clinical Classification of 24 MLH1 and MSH2 Gene Variants. Hum. Mutat. 2017, 38, 64–77. [Google Scholar] [CrossRef]
- Lindor, N.M.; Petersen, G.M.; Spurdle, A.B.; Thompson, B.; Goldgar, D.E.; Thibodeau, S.N. Pancreatic Cancer and a Novel MSH2 Germline Alteration. Pancreas 2011, 40, 1138–1140. [Google Scholar] [CrossRef]
- Cloyd, J.M.; Katz, M.H.G.; Wang, H.; Cuddy, A.; You, Y.N. Clinical and Genetic Implications of DNA Mismatch Repair Deficiency in Patients with Pancreatic Ductal Adenocarcinoma. JAMA Surg. 2017, 152, 1086–1088. [Google Scholar] [CrossRef]
- Riazy, M.; Kalloger, S.E.; Sheffield, B.S.; Peixoto, R.D.; Li-Chang, H.H.; Scudamore, C.H.; Renouf, D.J.; Schaeffer, D.F. Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma. Mod. Pathol. 2015, 28, 1383–1389. [Google Scholar] [CrossRef]
- Marcus, L.; Fashoyin-Aje, L.A.; Donoghue, M.; Yuan, M.; Rodriguez, L.; Gallagher, P.S.; Philip, R.; Ghosh, S.; Theoret, M.R.; Beaver, J.A.; et al. FDA Approval Summary: Pembrolizumab for the Treatment of Tumor Mutational Burden-High Solid Tumors. Clin. Cancer Res. 2021, 27, 4685–4689. [Google Scholar] [CrossRef] [PubMed]
- Ghidini, M.; Lampis, A.; Mirchev, M.B.; Okuducu, A.F.; Ratti, M.; Valeri, N.; Hahne, J.C. Immune-Based Therapies and the Role of Microsatellite Instability in Pancreatic Cancer. Genes 2020, 12, 33. [Google Scholar] [CrossRef] [PubMed]
- Forte, G.; Cariola, F.; De Marco, K.; Manghisi, A.; Guglielmi, F.A.; Armentano, R.; Lippolis, G.; Giorgio, P.; Simone, C.; Disciglio, V. A Novel STK11 Gene Mutation (c.388dupG, p.Glu130Glyfs∗33) in a Peutz-Jeghers Family and Evidence of Higher Gastric Cancer Susceptibility Associated with Alterations in STK11 Region Aa 107–170. Genes Dis. 2022, 9, 288–291. [Google Scholar] [CrossRef] [PubMed]
- Giardiello, F.M.; Welsh, S.B.; Hamilton, S.R.; Offerhaus, G.J.; Gittelsohn, A.M.; Booker, S.V.; Krush, A.J.; Yardley, J.H.; Luk, G.D. Increased Risk of Cancer in the Peutz-Jeghers Syndrome. N. Engl. J. Med. 1987, 316, 1511–1514. [Google Scholar] [CrossRef] [PubMed]
- Korsse, S.E.; Harinck, F.; van Lier, M.G.F.; Biermann, K.; Offerhaus, G.J.A.; Krak, N.; Looman, C.W.N.; van Veelen, W.; Kuipers, E.J.; Wagner, A.; et al. Pancreatic Cancer Risk in Peutz-Jeghers Syndrome Patients: A Large Cohort Study and Implications for Surveillance. J. Med. Genet. 2013, 50, 59–64. [Google Scholar] [CrossRef] [PubMed]
- Laderian, B.; Mundi, P.; Fojo, T.; Bates, S.E. Emerging Therapeutic Implications of STK11 Mutation: Case Series. Oncologist 2020, 25, 733–737. [Google Scholar] [CrossRef] [PubMed]
- Chan, S.H.; Chiang, J.; Ngeow, J. CDKN2A Germline Alterations and the Relevance of Genotype-Phenotype Associations in Cancer Predisposition. Hered. Cancer Clin. Pract. 2021, 19, 21. [Google Scholar] [CrossRef]
- De Snoo, F.A.; Bishop, D.T.; Bergman, W.; van Leeuwen, I.; van der Drift, C.; van Nieuwpoort, F.A.; Out-Luiting, C.J.; Vasen, H.F.; ter Huurne, J.A.; Frants, R.R.; et al. Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families. Clin. Cancer Res. 2008, 14, 7151–7157. [Google Scholar] [CrossRef]
- Vasen, H.F.; Gruis, N.A.; Frants, R.R.; van Der Velden, P.A.; Hille, E.T.; Bergman, W. Risk of Developing Pancreatic Cancer in Families with Familial Atypical Multiple Mole Melanoma Associated with a Specific 19 Deletion of P16 (P16-Leiden). Int. J. Cancer 2000, 87, 809–811. [Google Scholar] [CrossRef]
- Auroy, S.; Avril, M.F.; Chompret, A.; Pham, D.; Goldstein, A.M.; Bianchi-Scarrà, G.; Frebourg, T.; Joly, P.; Spatz, A.; Rubino, C.; et al. Sporadic Multiple Primary Melanoma Cases: CDKN2A Germline Mutations with a Founder Effect. Genes Chromosomes Cancer 2001, 32, 195–202. [Google Scholar] [CrossRef]
- Cremin, C.; Howard, S.; Le, L.; Karsan, A.; Schaeffer, D.F.; Renouf, D.; Schrader, K.A. CDKN2A Founder Mutation in Pancreatic Ductal Adenocarcinoma Patients without Cutaneous Features of Familial Atypical Multiple Mole Melanoma (FAMMM) Syndrome. Hered. Cancer Clin. Pract. 2018, 16, 7. [Google Scholar] [CrossRef] [PubMed]
- Borg, A.; Johannsson, U.; Johannsson, O.; Häkansson, S.; Westerdahl, J.; Mäsbäck, A.; Olsson, H.; Ingvar, C. Novel Germline P16 Mutation in Familial Malignant Melanoma in Southern Sweden. Cancer Res. 1996, 56, 2497–2500. [Google Scholar] [PubMed]
- Gruis, N.A.; van der Velden, P.A.; Sandkuijl, L.A.; Prins, D.E.; Weaver-Feldhaus, J.; Kamb, A.; Bergman, W.; Frants, R.R. Homozygotes for CDKN2 (P16) Germline Mutation in Dutch Familial Melanoma Kindreds. Nat. Genet. 1995, 10, 351–353. [Google Scholar] [CrossRef] [PubMed]
- Lang, J.; Hayward, N.; Goldgar, D.; Tsao, H.; Hogg, D.; Palmer, J.; Stark, M.; Tobias, E.S.; MacKie, R. The M53I Mutation in CDKN2A Is a Founder Mutation That Predominates in Melanoma Patients with Scottish Ancestry. Genes Chromosomes Cancer 2007, 46, 277–287. [Google Scholar] [CrossRef] [PubMed]
- Al Baghdadi, T.; Halabi, S.; Garrett-Mayer, E.; Mangat, P.K.; Ahn, E.R.; Sahai, V.; Alvarez, R.H.; Kim, E.S.; Yost, K.J.; Rygiel, A.L.; et al. Palbociclib in Patients with Pancreatic and Biliary Cancer with CDKN2A Alterations: Results From the Targeted Agent and Profiling Utilization Registry Study. JCO Precis. Oncol. 2019, 3, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Shaya, J.; Kato, S.; Adashek, J.J.; Patel, H.; Fanta, P.T.; Botta, G.P.; Sicklick, J.K.; Kurzrock, R. Personalized Matched Targeted Therapy in Advanced Pancreatic Cancer: A Pilot Cohort Analysis. NPJ Genom. Med. 2023, 8, 1. [Google Scholar] [CrossRef] [PubMed]
- Maddalena, M.; Mallel, G.; Nataraj, N.B.; Shreberk-Shaked, M.; Hassin, O.; Mukherjee, S.; Arandkar, S.; Rotkopf, R.; Kapsack, A.; Lambiase, G.; et al. TP53 Missense Mutations in PDAC Are Associated with Enhanced Fibrosis and an Immunosuppressive Microenvironment. Proc. Natl. Acad. Sci. USA 2021, 118, e2025631118. [Google Scholar] [CrossRef]
- Senzer, N.; Nemunaitis, J.; Nemunaitis, D.; Bedell, C.; Edelman, G.; Barve, M.; Nunan, R.; Pirollo, K.F.; Rait, A.; Chang, E.H. Phase I Study of a Systemically Delivered P53 Nanoparticle in Advanced Solid Tumors. Mol. Ther. 2013, 21, 1096–1103. [Google Scholar] [CrossRef]
- Gao, J.; Chen, X.; Li, X.; Miao, F.; Fang, W.; Li, B.; Qian, X.; Lin, X. Differentiating TP53 Mutation Status in Pancreatic Ductal Adenocarcinoma Using Multiparametric MRI-Derived Radiomics. Front. Oncol. 2021, 11, 632130. [Google Scholar] [CrossRef]
- Yap, T.A.; Stadler, Z.K.; Stout, L.A.; Schneider, B.P. Aligning Germline Cancer Predisposition with Tumor-Based Next-Generation Sequencing for Modern Oncology Diagnosis, Interception, and Therapeutic Development. Am. Soc. Clin. Oncol. Educ. Book 2023, 43, e390738. [Google Scholar] [CrossRef]
- Taeubner, J.; Wieczorek, D.; Yasin, L.; Brozou, T.; Borkhardt, A.; Kuhlen, M. Penetrance and Expressivity in Inherited Cancer Predisposing Syndromes. Trends Cancer 2018, 4, 718–728. [Google Scholar] [CrossRef] [PubMed]
- Turchiano, A.; Piglionica, M.; Martino, S.; Bagnulo, R.; Garganese, A.; De Luisi, A.; Chirulli, S.; Iacoviello, M.; Stasi, M.; Tabaku, O.; et al. Impact of High-to-Moderate Penetrance Genes on Genetic Testing: Looking over Breast Cancer. Genes 2023, 14, 1530. [Google Scholar] [CrossRef] [PubMed]
- Nolano, A.; Medugno, A.; Trombetti, S.; Liccardo, R.; De Rosa, M.; Izzo, P.; Duraturo, F. Hereditary Colorectal Cancer: State of the Art in Lynch Syndrome. Cancers 2022, 15, 75. [Google Scholar] [CrossRef] [PubMed]
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Pantaleo, A.; Forte, G.; Fasano, C.; Lepore Signorile, M.; Sanese, P.; De Marco, K.; Di Nicola, E.; Latrofa, M.; Grossi, V.; Disciglio, V.; et al. Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review. Cancers 2024, 16, 56. https://doi.org/10.3390/cancers16010056
Pantaleo A, Forte G, Fasano C, Lepore Signorile M, Sanese P, De Marco K, Di Nicola E, Latrofa M, Grossi V, Disciglio V, et al. Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review. Cancers. 2024; 16(1):56. https://doi.org/10.3390/cancers16010056
Chicago/Turabian StylePantaleo, Antonino, Giovanna Forte, Candida Fasano, Martina Lepore Signorile, Paola Sanese, Katia De Marco, Elisabetta Di Nicola, Marialaura Latrofa, Valentina Grossi, Vittoria Disciglio, and et al. 2024. "Understanding the Genetic Landscape of Pancreatic Ductal Adenocarcinoma to Support Personalized Medicine: A Systematic Review" Cancers 16, no. 1: 56. https://doi.org/10.3390/cancers16010056