作者
Theo A Knijnenburg, Linghua Wang, Michael T Zimmermann, Nyasha Chambwe, Galen F Gao, Andrew D Cherniack, Huihui Fan, Hui Shen, Gregory P Way, Casey S Greene, Yuexin Liu, Rehan Akbani, Bin Feng, Lawrence A Donehower, Chase Miller, Yang Shen, Mostafa Karimi, Haoran Chen, Pora Kim, Peilin Jia, Eve Shinbrot, Shaojun Zhang, Jianfang Liu, Hai Hu, Matthew H Bailey, Christina Yau, Denise Wolf, Zhongming Zhao, John N Weinstein, Lei Li, Li Ding, Gordon B Mills, Peter W Laird, David A Wheeler, Ilya Shmulevich, Raymond J Monnat Jr, Yonghong Xiao, Chen Wang, Cancer Genome Atlas Research Network
发表日期
2018/4/3
期刊
Cell reports
卷号
23
期号
1
页码范围
239
出版商
NIH Public Access
简介
DNA damage repair (DDR) pathways modulate cancer risk, progression, and therapeutic response. We systematically analyzed somatic alterations to provide a comprehensive view of DDR deficiency across 33 cancer types. Mutations with accompanying loss of heterozygosity were observed in over 1/3 of DDR genes, including TP53 and BRCA1/2. Other prevalent alterations included epigenetic silencing of the direct repair genes EXO5, MGMT, and ALKBH3 in ∼20% of samples. Homologous recombination deficiency (HRD) was present at varying frequency in many cancer types, most notably ovarian cancer. However, in contrast to ovarian cancer, HRD was associated with worse outcomes in several other cancers. Protein structure-based analyses allowed us to predict functional consequences of rare, recurrent DDR mutations. A new machine-learning-based classifier developed from gene expression data …
学术搜索中的文章
TA Knijnenburg, L Wang, MT Zimmermann… - Cell reports, 2018