作者
Helen Davies, Dominik Glodzik, Sandro Morganella, Lucy R Yates, Johan Staaf, Xueqing Zou, Manasa Ramakrishna, Sancha Martin, Sandrine Boyault, Anieta M Sieuwerts, Peter T Simpson, Tari A King, Keiran Raine, Jorunn E Eyfjord, Gu Kong, Åke Borg, Ewan Birney, Hendrik G Stunnenberg, Marc J Van De Vijver, Anne-Lise Børresen-Dale, John WM Martens, Paul N Span, Sunil R Lakhani, Anne Vincent-Salomon, Christos Sotiriou, Andrew Tutt, Alastair M Thompson, Steven Van Laere, Andrea L Richardson, Alain Viari, Peter J Campbell, Michael R Stratton, Serena Nik-Zainal
发表日期
2017/4
期刊
Nature medicine
卷号
23
期号
4
页码范围
517-525
出版商
Nature Publishing Group US
简介
Approximately 1–5% of breast cancers are attributed to inherited mutations in BRCA1 or BRCA2 and are selectively sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors. In other cancer types, germline and/or somatic mutations in BRCA1 and/or BRCA2 (BRCA1/BRCA2) also confer selective sensitivity to PARP inhibitors. Thus, assays to detect BRCA1/BRCA2-deficient tumors have been sought. Recently, somatic substitution, insertion/deletion and rearrangement patterns, or 'mutational signatures', were associated with BRCA1/BRCA2 dysfunction. Herein we used a lasso logistic regression model to identify six distinguishing mutational signatures predictive of BRCA1/BRCA2 deficiency. A weighted model called HRDetect was developed to accurately detect BRCA1/BRCA2-deficient samples. HRDetect identifies BRCA1/BRCA2-deficient tumors with 98.7% sensitivity (area under the curve (AUC) = 0.98 …
学术搜索中的文章
H Davies, D Glodzik, S Morganella, LR Yates, J Staaf… - Nature medicine, 2017