Integrated somatic and germline whole-exome sequencing analysis inwomen with lung cancer after a previous breast cancer

S Coco, S Bonfiglio, D Cittaro, I Vanni, M Mora, C Genova, MGD Bello, S Boccardo, A Alama, E Rijavec, C Sini, V Rossella, G Barletta, F Biello, A Truini, C Bruzzo, M Gallo, D Lazarevic, A Ballestrero, F Grossi

Research output: Contribution to journalArticlepeer-review

Abstract

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 from28/60 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 and16/28 LCs, and S2 (C>A) which is strongly associated with smoking, in12/28 LCs. The burden test over rare germline variants in S1-LC vs CP identified248 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 © 2019 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
JournalCancers
Volume11
Issue number4
DOIs
Publication statusPublished - 2019

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