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

Simona Coco, Silvia Bonfiglio, Davide Cittaro, Irene Vanni, Marco Mora, Carlo Genova, Maria Giovanna Dal Bello, Simona Boccardo, Angela Alama, Erika Rijavec, Claudio Sini, Valeria Rossella, Giulia Barletta, Federica Biello, Anna Truini, Cristina Bruzzo, Maurizio Gallo, Dejan Lazarevic, Alberto Ballestrero, Francesco Grossi

Research output: Contribution to journalArticle

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

Original languageEnglish
Article number441
JournalCancers
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 1 2019

Keywords

  • Breast cancer
  • Exome sequencing
  • Genetic predisposition
  • Lung cancer
  • Multiple cancer susceptibility

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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