Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
Landscape of somatic mutations in 560 breast cancer whole-genome sequences.
复制标题
DOI：
10.1038/nature17676
复制
发表时间：
2016-06-02
期刊：
影响因子：
64.8
通讯作者：
Stratton MR
中科院分区：
文献类型：
--
作者：
Nik-Zainal S;Davies H;Staaf J;Ramakrishna M;Glodzik D;Zou X;Martincorena I;Alexandrov LB;Martin S;Wedge DC;Van Loo P;Ju YS;Smid M;Brinkman AB;Morganella S;Aure MR;Lingjærde OC;Langerød A;Ringnér M;Ahn SM;Boyault S;Brock JE;Broeks A;Butler A;Desmedt C;Dirix L;Dronov S;Fatima A;Foekens JA;Gerstung M;Hooijer GK;Jang SJ;Jones DR;Kim HY;King TA;Krishnamurthy S;Lee HJ;Lee JY;Li Y;McLaren S;Menzies A;Mustonen V;O'Meara S;Pauporté I;Pivot X;Purdie CA;Raine K;Ramakrishnan K;Rodríguez-González FG;Romieu G;Sieuwerts AM;Simpson PT;Shepherd R;Stebbings L;Stefansson OA;Teague J;Tommasi S;Treilleux I;Van den Eynden GG;Vermeulen P;Vincent-Salomon A;Yates L;Caldas C;van't Veer L;Tutt A;Knappskog S;Tan BK;Jonkers J;Borg Å;Ueno NT;Sotiriou C;Viari A;Futreal PA;Campbell PJ;Span PN;Van Laere S;Lakhani SR;Eyfjord JE;Thompson AM;Birney E;Stunnenberg HG;van de Vijver MJ;Martens JW;Børresen-Dale AL;Richardson AL;Kong G;Thomas G;Stratton MR
我们分析了560例乳腺癌的全基因组序列，以促进对赋予克隆优势的驱动突变和产生体细胞突变的突变过程的理解。93个编码蛋白质的癌症基因携带可能的驱动突变。一些非编码区表现出很高的突变频率，但大多数都有独特的结构特征，可能会导致突变率上升，并且不存在驱动突变。突变特征分析扩展到基因组重排，发现了12个碱基替换和6个重排特征。以串联复制或缺失为特征的三个重排特征与基于同源重组的DNA修复缺陷有关：一个具有BRCA1功能缺陷；另一个BRCA1或BRCA2功能缺陷；第三个原因未知。这种跨越外显子、内含子和基因间隔区的各类体细胞突变的分析突出了癌症基因和操作的突变过程的保留，并朝着全面解释乳腺癌的体细胞遗传学基础的方向发展。
We analysed whole genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. 93 protein-coding cancer genes carried likely driver mutations. Some non-coding regions exhibited high mutation frequencies but most have distinctive structural features probably causing elevated mutation rates and do not harbour driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed 12 base substitution and six rearrangement signatures. Three rearrangement signatures, characterised by tandem duplications or deletions, appear associated with defective homologous recombination based DNA repair: one with deficient BRCA1 function; another with deficient BRCA1 or BRCA2 function; the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operative, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer.