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, Samantha J Caesar-Johnson, John A Demchok, Ina Felau, Melpomeni Kasapi, Martin L Ferguson, Carolyn M Hutter, Heidi J Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C Zenklusen, Jiashan Julia Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I Heiman, Jaegil Kim, Michael S Lawrence, Pei Lin, Sam Meier, Michael S Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Michael Miller, Sheila Reynolds, Vesteinn Thorsson, Wei Zhang, Bradley M Broom, Apurva M Hegde, Zhenlin Ju, Rupa S Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E Gross, Zachary J Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G Nissan, Angelica Ochoa, Sarah M Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S Onur Sumer, Yichao Sun, Barry S Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Joshua M Stuart, Christopher K Wong, D Neil Hayes, Joel S Parker, Matthew D Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven JM Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A Marra, Michael Mayo, Richard A Moore, Andrew J Mungall, Karen Mungall, A Gordon Robertson, Sara Sadeghi, Jacqueline E Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen
发表日期
2018/4/3
期刊
Cell reports
卷号
23
期号
1
页码范围
239-254. e6
出版商
Elsevier
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 …
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