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Article

Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer

1
Lung Cancer Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
2
Centre for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy
3
Department of Internal Medicine and Medical Specialties (DIMI), University of Genoa, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
4
Department of Pathology, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
5
Swiss Stem Cell Biotech, 6830 Vacallo, Switzerland
6
UOC Oncologia Medica Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Cancers 2019, 11(4), 441; https://doi.org/10.3390/cancers11040441
Received: 8 February 2019 / Revised: 12 March 2019 / Accepted: 25 March 2019 / Published: 28 March 2019
(This article belongs to the Special Issue Application of Next-Generation Sequencing in Cancers)
Women treated for breast cancer (BC) are at risk of developing secondary tumors, such as lung cancer (LC). Since rare germline variants have been linked to multiple cancer development, we hypothesized that BC survivors might be prone to develop LC as a result of harboring rare variants. Sixty patients with LC with previous BC (the study population; SP) and 53 women with either BC or LC and no secondary cancer (control population; CP) were enrolled. Whole exome sequencing was performed in both tumors and unaffected tissues from 28/60 SP patients, and in germline DNA from 32/53 CP. Candidate genes were validated in the remaining individuals from both populations. We found two main mutational signature profiles: S1 (C>T) in all BCs and 16/28 LCs, and S2 (C>A) which is strongly associated with smoking, in 12/28 LCs. The burden test over rare germline variants in S1-LC vs CP identified 248 genes. Validation confirmed GSN as significantly associated with LC in never-smokers. In conclusion, our data suggest two signatures involved in LC onset in women with previous BC. One of these signatures is linked to smoking. Conversely, regardless of smoking habit, in a subgroup of BC survivors genetic susceptibility may contribute to LC risk. View Full-Text
Keywords: breast cancer; lung cancer; multiple cancer susceptibility; genetic predisposition; exome sequencing breast cancer; lung cancer; multiple cancer susceptibility; genetic predisposition; exome sequencing
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MDPI and ACS Style

Coco, S.; Bonfiglio, S.; Cittaro, D.; Vanni, I.; Mora, M.; Genova, C.; Dal Bello, M.G.; Boccardo, S.; Alama, A.; Rijavec, E.; Sini, C.; Rossella, V.; Barletta, G.; Biello, F.; Truini, A.; Bruzzo, C.; Gallo, M.; Lazarevic, D.; Ballestrero, A.; Grossi, F. Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer. Cancers 2019, 11, 441. https://doi.org/10.3390/cancers11040441

AMA Style

Coco S, Bonfiglio S, Cittaro D, Vanni I, Mora M, Genova C, Dal Bello MG, Boccardo S, Alama A, Rijavec E, Sini C, Rossella V, Barletta G, Biello F, Truini A, Bruzzo C, Gallo M, Lazarevic D, Ballestrero A, Grossi F. Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer. Cancers. 2019; 11(4):441. https://doi.org/10.3390/cancers11040441

Chicago/Turabian Style

Coco, Simona; Bonfiglio, Silvia; Cittaro, Davide; Vanni, Irene; Mora, Marco; Genova, Carlo; Dal Bello, Maria G.; Boccardo, Simona; Alama, Angela; Rijavec, Erika; Sini, Claudio; Rossella, Valeria; Barletta, Giulia; Biello, Federica; Truini, Anna; Bruzzo, Cristina; Gallo, Maurizio; Lazarevic, Dejan; Ballestrero, Alberto; Grossi, Francesco. 2019. "Integrated Somatic and Germline Whole-Exome Sequencing Analysis in Women with Lung Cancer after a Previous Breast Cancer" Cancers 11, no. 4: 441. https://doi.org/10.3390/cancers11040441

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