The Role of Circulating Tumor DNA and Cell-Free DNA in the Management of Germ Cell Tumors: A Narrative Review
Abstract
:1. Introduction
2. Methods
2.1. Circulating Tumor DNA and Cell-Free DNA in Testicular Cancer
2.2. Clinical Utility of Circulating Tumor DNA and Cell-Free DNA in Testicular Cancer
3. Discussion
Conflicts of Interest
Abbreviations
AFP | alpha-fetoprotein |
bp | base pairs |
CTCs | circulating tumor cells |
cfDNA | cell-free DNA |
ctDNA | circulating tumor DNA |
GCTs | germ cell tumors |
hCG | human chorionic gonadotropin |
LDH | lactate dehydrogenase |
miRNA | microRNA |
PCR | polymerase chain reaction |
qPCR | quantitative polymerase chain reaction |
RT-PCR | reverse transcription-polymerase chain reaction |
TGCTs | testicular germ cell tumors |
References
- Ellinger, J.; Wittkamp, V.; Albers, P.; Perabo, F.G.E.; Mueller, S.C.; von Ruecker, A.; et al. Cell-free circulating DNA: diagnostic value in patients with testicular germ cell cancer. J. Urol. 2009, 181, 363–371. [Google Scholar] [CrossRef] [PubMed]
- Trigo, J.M.; Tabernero, J.M.; Paz-Ares, L.; García-Llano, J.L.; Mora, J.; Lianes, P.; et al. Tumor markers at the time of recurrence in patients with germ cell tumors. Cancer 2000, 88, 162–168. [Google Scholar] [CrossRef] [PubMed]
- Lobo, J.; Gillis, A.J.M.; Jerónimo, C.; Henrique, R.; Looijenga, L.H.J. Human germ cell tumors are developmental cancers: impact of epigenetics on pathobiology and clinic. Int. J. Mol. Sci. 2019, 20, 258. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Russano, M.; Napolitano, A.; Ribelli, G.; Iuliani, M.; Simonetti, S.; Citarella, F.; et al. Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples. J. Exp. Clin. Cancer Res. 2020, 39, 95. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Russano, M.; Napolitano, A.; Ribelli, G.; Iuliani, M.; Simonetti, S.; Citarella, F.; et al. Liquid biopsy and tumor heterogeneity in metastatic solid tumors: the potentiality of blood samples. J. Exp. Clin. Cancer Res. 2020, 39, 95. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Geeurickx, E.; Hendrix, A. Targets, pitfalls and reference materials for liquid biopsy tests in cancer diagnostics. Mol. Aspects Med. 2020, 72, 100828. [Google Scholar] [CrossRef] [PubMed]
- Geeurickx, E.; Hendrix, A. Targets, pitfalls and reference materials for liquid biopsy tests in cancer diagnostics. Mol. Aspects Med. 2020, 72, 100828. [Google Scholar] [CrossRef] [PubMed]
- Pal, S.K.; Rosenberg, J.E.; Hoffman-Censits, J.H.; Berger, R.; Quinn, D.I.; Galsky, M.D.; et al. Efficacy of BGJ398, a fibroblast growth factor receptor 1–3 inhibitor, in patients with previously treated advanced urothelial carcinoma with FGFR3 alterations. Cancer Discov. 2018, 8, 812–821. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Powles, T.; Carroll, D.; Chowdhury, S.; Gravis, G.; Joly, F.; Carles, J.; et al. An adaptive, biomarker-directed platform study of durvalumab in combination with targeted therapies in advanced urothelial cancer. Nat. Med. 2021, 27, 793–801. [Google Scholar] [CrossRef] [PubMed]
- RenJi Hospital. Circulating Tumour DNA and Urine Tumor DNA Detection of Minimal Residual Disease in Locally Advanced Upper Tract Urothelial Carcinoma With Radical Nephroureterectomy: A Cohort Study. CinicalTrials.gov identifier NCT05595408. Updated , 2022. Available online: https://clinicaltrials.gov/ct2/show/NCT05595408 (accessed on 6 March 2023).
- The Netherlands Cancer Institute. Phase 1B Study to Assess Safety and Efficacy of Neo-Adjuvant Bladder Urothelial Carcinoma Combination-immunotherapy (NABUCCO). CinicalTrials.gov identifier NCT03387761. Updated April 28, 2022. Available online: https://clinicaltrials.gov/ct2/show/NCT03387761 (accessed on 6 March 2023).
- Lolkema, M.P.J.K.; Erasmus Medical Center. Biomarker Discovery Study to Identify Patients With Advanced Urothelial Cancer Benefitting From Pembrolizumab Treatment. CinicalTrials.gov identifier NCT03263039. Updated August 20, 2021. Available online: https://clinicaltrials.gov/ct2/show/NCT03263039 (accessed on 6 March 2023).
- Krasic, J.; Skara, L.; Bojanac, A.K.; Ulamec, M.; Jezek, D.; Kulis, T.; et al. The utility of cfDNA in TGCT patient management: a systematic review. Ther. Adv. Med. Oncol. 2022, 14, 17588359221090365. [Google Scholar] [CrossRef] [PubMed]
- Boublikova, L.; Kramarzova, K.S.; Zwyrtkova, M.; Bakardjieva-Mihaylova, V.; Stuchly, J.; Rosova, B.; et al. The clinical value of circulating free tumor DNA in testicular germ cell tumor patients. Urol. Oncol. 2022, 40, 412.e15–412.e24. [Google Scholar] [CrossRef] [PubMed]
- Bokemeyer, C.; Gillis, A.J.; Pompe, K.; Mayer, F.; Metzner, B.; Schleucher, N.; et al. Clinical impact of germ cell tumor cells in apheresis products of patients receiving high-dose chemotherapy. J. Clin. Oncol. 2001, 19, 3029–3036. [Google Scholar] [CrossRef] [PubMed]
- Fan, Y.; Einhorn, L.; Saxman, S.; Katz, B.; Abonour, R.; Cornetta, K. Detection of germ cell tumor cells in apheresis products using polymerase chain reaction. Clin. Cancer Res. 1998, 4, 93–98. [Google Scholar] [PubMed]
- Hautkappe, A.L.; Lu, M.; Mueller, H.; Bex, A.; Harstrick, A.; Roggendorf, M.; et al. Detection of germ-cell tumor cells in the peripheral blood by nested reverse transcription-polymerase chain reaction for α-fetoprotein-messenger RNA and ß human chorionic gonadotropin-messenger RNA1. Cancer Res. 2000, 60, 3170–3174. [Google Scholar] [PubMed]
- Hildebrandt, M.O.; Bläser, F.; Beyer, J.; Siegert, W.; Mapara, M.Y.; Huhn, D.; et al. Detection of tumor cells in peripheral blood samples from patients with germ cell tumors using immunocytochemical and reverse transcriptase-polymerase chain reaction techniques. Bone Marrow Transplant. 1998, 22, 771–775. [Google Scholar] [CrossRef] [PubMed]
- Yuasa, T.; Yoshiki, T.; Tanaka, T.; Isono, T.; Okada, Y. Detection of circulating testicular cancer cells in peripheral blood. Cancer Lett. 1999, 143, 57–62. [Google Scholar] [CrossRef] [PubMed]
- Nastały, P.; Ruf, C.; Becker, P.; Bednarz-Knoll, N.; Stoupiec, M.; Kavsur, R.; et al. Circulating tumor cells in patients with testicular germ cell tumors. Clin. Cancer Res. 2014, 20, 3830–3841. [Google Scholar] [CrossRef] [PubMed]
- Ruf, C.; Nastały, P.; Becker, P.; Isbarn, H.; Honecker, F.; Pantel, K.; et al. 703 Circulating tumor cells can be detected in patients with testicular germ cell tumors. J. Urol. 2013, 189, e289. [Google Scholar] [CrossRef]
- Lobo, J.; van Zogchel, L.M.J.; Nuru, M.G.; Gillis, A.J.M.; van der Schoot, C.E.; Tytgat, G.A.M.; et al. Combining hypermethylated RASSF1A detection using ddPCR with miR-371a-3p testing: an improved panel of liquid biopsy biomarkers for testicular germ cell tumor patients. Cancers (Basel) 2021, 13, 5228. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Ellinger, J.; Albers, P.; Perabo, F.G.; Müller, S.C.; von Ruecker, A.; Bastian, P.J. CpG island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer. J. Urol. 2009, 182, 324–329. [Google Scholar] [CrossRef] [PubMed]
- Kawakami, T.; Okamoto, K.; Ogawa, O.; Okada, Y. XIST unmethylated DNA fragments in male-derived plasma as a tumour marker for testicular cancer. Lancet 2004, 363, 40–42. [Google Scholar] [CrossRef] [PubMed]
- Ellinger, J.; Albers, P.; Müller, S.C.; von Ruecker, A.; Bastian, P.J. Circulating mitochondrial DNA in the serum of patients with testicular germ cell cancer as a novel noninvasive diagnostic biomarker. BJU Int. 2009, 104, 48–52. [Google Scholar] [CrossRef] [PubMed]
- Tsui, D.W.Y.; Cheng, M.L.; Shady, M.; Yang, J.L.; Stephens, D.; Won, H.; et al. Tumor fraction-guided cell-free DNA profiling in metastatic solid tumor patients. Genome Med. 2021, 13, 96. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Royal Marsden NHS Foundation Trust. Exploratory Study of Molecular Characterization in Patients With Metastatic Germ Cell Tumours Refractory/Resistant to Platinum Treatment. CinicalTrials.gov identifier NCT03980587. Updated June 10, 2019. Available online: https://clinicaltrials.gov/ct2/show/NCT03980587 (accessed on 11 June 2023).
- Lavoie, J.M.; Kollmannsberger, C.K. Current management of disseminated germ cell tumors. Urol. Clin. North. Am. 2019, 46, 377–388. [Google Scholar] [CrossRef] [PubMed]
- Murray, M.J.; Halsall, D.J.; Hook, C.E.; Williams, D.M.; Nicholson, J.C.; Coleman, N. Identification of microRNAs from the miR-371~373 and miR-302 clusters as potential serum biomarkers of malignant germ cell tumors. Am. J. Clin. Pathol. 2011, 135, 119–125. [Google Scholar] [CrossRef] [PubMed]
- Gillis, A.J.M.; Rijlaarsdam, M.A.; Eini, R.; Dorssers, L.C.J.; Biermann, K.; Murray, M.J.; et al. Targeted serum miRNA (TSmiR) test for diagnosis and follow-up of (testicular) germ cell cancer patients: a proof of principle. Mol. Oncol. 2013, 7, 1083–1092. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Dieckmann, K.P.; Radtke, A.; Geczi, L.; Matthies, C.; Anheuser, P.; Eckardt, U.; et al. Serum levels of microRNA-371a-3p (M371 Test) as a new biomarker of testicular germ cell tumors: results of a prospective multicentric study. J. Clin. Oncol. 2019, 37, 1412–1423. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Nappi, L.; Thi, M.; Lum, A.; Huntsman, D.; Eigl, B.J.; Martin, C.; et al. Developing a highly specific biomarker for germ cell malignancies: plasma miR371 expression across the germ cell malignancy spectrum. J. Clin. Oncol. 2019, 37, 3090–3098. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Lafin, J.T.; Singla, N.; Woldu, S.L.; Lotan, Y.; Lewis, C.M.; Majmudar, K.; et al. Serum microRNA-371a-3p levels predict viable germ cell tumor in chemotherapy-naïve patients undergoing retroperitoneal lymph node dissection. Eur. Urol. 2020, 77, 290–292. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Leão, R.; van Agthoven, T.; Figueiredo, A.; Jewett, M.A.S.; Fadaak, K.; Sweet, J.; et al. Serum miRNA predicts viable disease after chemotherapy in patients with testicular nonseminoma germ cell tumor. J. Urol. 2018, 200, 126–135. [Google Scholar] [CrossRef] [PubMed]
- Haukeland University Hospital. MicroRNA as Markers in Testicular Cancer. ClinicalTrials.gov identifier NCT04914026. Updated August 8, 2022. Available online: https://clinicaltrials.gov/ct2/show/NCT04914026?cond=NCT04914026 (accessed on 11 June 2023).
- SWOG Cancer Research Network. A Study of miRNA 371 in Patients With Germ Cell Tumors. ClinicalTrials.gov identifier NCT04435756. Updated June 9, 2023. Available online: https://clinicaltrials.gov/ct2/show/NCT04435756 (accessed on 11 June 2023).
- Merker, J.D.; Oxnard, G.R.; Compton, C.; Diehn, M.; Hurley, P.; Lazar, A.J.; et al. Circulating tumor DNA analysis in patients with cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. J. Clin. Oncol. 2018, 36, 1631–1641. [Google Scholar] [CrossRef] [PubMed]
- Fleischhacker, M.; Schmidt, B. Pre-analytical issues in liquid biopsy – where do we stand? J. Lab. Med. 2020, 44, 117–142. [Google Scholar] [CrossRef]
- Ellervik, C.; Vaught, J. Preanalytical variables affecting the integrity of human biospecimens in biobanking. Clin. Chem. 2015, 61, 914–934. [Google Scholar] [CrossRef] [PubMed]
This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited. © 2023 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.
Share and Cite
Dolendo, I.; Cox, S.; Puri, D.; Bagrodia, A. The Role of Circulating Tumor DNA and Cell-Free DNA in the Management of Germ Cell Tumors: A Narrative Review. Soc. Int. Urol. J. 2023, 4, 293-300. https://doi.org/10.48083/IPCO3495
Dolendo I, Cox S, Puri D, Bagrodia A. The Role of Circulating Tumor DNA and Cell-Free DNA in the Management of Germ Cell Tumors: A Narrative Review. Société Internationale d’Urologie Journal. 2023; 4(4):293-300. https://doi.org/10.48083/IPCO3495
Chicago/Turabian StyleDolendo, Isabella, Shanice Cox, Dhruv Puri, and Aditya Bagrodia. 2023. "The Role of Circulating Tumor DNA and Cell-Free DNA in the Management of Germ Cell Tumors: A Narrative Review" Société Internationale d’Urologie Journal 4, no. 4: 293-300. https://doi.org/10.48083/IPCO3495
APA StyleDolendo, I., Cox, S., Puri, D., & Bagrodia, A. (2023). The Role of Circulating Tumor DNA and Cell-Free DNA in the Management of Germ Cell Tumors: A Narrative Review. Société Internationale d’Urologie Journal, 4(4), 293-300. https://doi.org/10.48083/IPCO3495