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A genomic copy number signature predicts radiation exposure in post‐ C hernobyl breast cancer
Author(s) -
Wilke Christina M.,
Braselmann Herbert,
Hess Julia,
Klymenko Sergiy V.,
Chumak Vadim V.,
Zakhartseva Liubov M.,
Bakhanova Elena V.,
Walch Axel K.,
Selmansberger Martin,
Samaga Daniel,
Weber Peter,
Schneider Ludmila,
Fend Falko,
Bösmüller Hans C.,
Zitzelsberger Horst,
Unger Kristian
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31533
Subject(s) - breast cancer , cancer , comparative genomic hybridization , copy number variation , ionizing radiation , oncology , biology , medicine , cancer research , genetics , gene , genome , irradiation , nuclear physics , physics
Breast cancer is the second leading cause of cancer death among women worldwide and besides life style, age and genetic risk factors, exposure to ionizing radiation is known to increase the risk for breast cancer. Further, DNA copy number alterations (CNAs), which can result from radiation‐induced double‐strand breaks, are frequently occurring in breast cancer cells. We set out to identify a signature of CNAs discriminating breast cancers from radiation‐exposed and non‐exposed female patients. We analyzed resected breast cancer tissues from 68 exposed female Chernobyl clean‐up workers and evacuees and 68 matched non‐exposed control patients for CNAs by array comparative genomic hybridization analysis (aCGH). Using a stepwise forward–backward selection approach a non‐complex CNA signature, that is, less than ten features, was identified in the training data set, which could be subsequently validated in the validation data set ( p value < 0.05). The signature consisted of nine copy number regions located on chromosomal bands 7q11.22‐11.23, 7q21.3, 16q24.3, 17q21.31, 20p11.23‐11.21, 1p21.1, 2q35, 2q35, 6p22.2. The signature was independent of any clinical characteristics of the patients. In all, we identified a CNA signature that has the potential to allow identification of radiation‐associated breast cancer at the individual level.