signature=091d876c3fb53658fc37bc5ef806e157,Signatures of mutational processes in human cancer

摘要：

All cancers are caused by somatic mutations; however, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single cancer class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA malntenance,but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, 'kataegis' , is found in many cancer types. The results reveal the diversity of mutational process underlying the development of cancer, with potential implications for understanding of cancer aetiology, prevention and therapy.%尽管所有癌症都被认为是由体细胞突变(身体 中除生殖细胞以外的任何细胞的突变)造成 的,但我们对所涉及的突变过程相对来说却rn知之甚少。这项研究分析了来自超过7,000癌 症的近500万突变,发现了超过20个与癌症相 关的不同突变特征。这些特征中有些存在于 很多癌症中,其中一个特征属于APOBEC家 族的胞苷脱氨酶,而其他特征则是个别肿瘤 类型特有的。有些特征与年龄、已知诱变因 素或DNA维护中的缺陷有关,但很多的来源 却很神秘。这些发现对于了解癌症病因、预 防和治疗有潜在意义。

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