A mutational signature in gastric cancer suggests therapeutic strategies

被引：154

作者：

Alexandrov, Ludmil B. ^{[1
,2
,3
]}

Nik-Zainal, Serena ^{[1
,4
]}

Siu, Hoi Cheong ^{[5
]}

Leung, Suet Yi ^{[5
]}

Stratton, Michael R. ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Canc Genome Project, Hinxton CB10 1SA, Cambs, England

[2] Los Alamos Natl Lab, Theoret Biol & Biophys T6, Los Alamos, NM 87545 USA

[3] Los Alamos Natl Lab, Ctr Nonlinear Studies, Los Alamos, NM 87545 USA

[4] Addenbrookes Hosp Natl Hlth Serv NHS Trust, Dept Med Genet, Cambridge CB2 2QQ, England

[5] Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Pokfulam, Hong Kong, Peoples R China

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

英国惠康基金; 美国能源部;

关键词：

SOMATIC MUTATIONS; BRCA2; MUTATIONS; BREAST; REVEALS; PENETRANCE; GENOMES; ORIGIN; CELLS;

D O I：

10.1038/ncomms9683

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Targeting defects in the DNA repair machinery of neoplastic cells, for example, those due to inactivating BRCA1 and/or BRCA2 mutations, has been used for developing new therapies in certain types of breast, ovarian and pancreatic cancers. Recently, a mutational signature was associated with failure of double-strand DNA break repair by homologous recombination based on its high mutational burden in samples harbouring BRCA1 or BRCA2 mutations. In pancreatic cancer, all responders to platinum therapy exhibit this mutational signature including a sample that lacked any defects in BRCA1 or BRCA2. Here, we examine 10,250 cancer genomes across 36 types of cancer and demonstrate that, in addition to breast, ovarian and pancreatic cancers, gastric cancer is another cancer type that exhibits this mutational signature. Our results suggest that 7-12% of gastric cancers have defective double-strand DNA break repair by homologous recombination and may benefit from either platinum therapy or PARP inhibitors.

引用

页数：7

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