Nature2014-06-26 4:46 PM

新的癌症基因被发现 Discovery and saturation analysis of cancer genes across 21 tumour types

论文摘要 

大多数癌症基因都是以中等频率发生突变的,在某一具体肿瘤类型的五个样本中发生突变的不到一个,所以对癌症基因的准确识别需要基于大规模取样,以便将突变率的这种异质性考虑进去。这项研究对来自超过4700个“肿瘤-正常对”的21个肿瘤类型进行了统计分析。作者识别出33个以前不知道的基因,它们与增殖、凋亡、基因组不稳定、染色质调控、免疫逃避、RNA处理和蛋白动态平衡有关。进一步的分析表明,对某一给定的肿瘤类型,600到5000个样本也许能达到近乎饱和的程度,具体情况取决于背景突变速度。

Abstract 

Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2–20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and their matched normal-tissue samples across 21 cancer types. We found that large-scale genomic analysis can identify nearly all known cancer genes in these tumour types. Our analysis also identified 33 genes that were not previously known to be significantly mutated in cancer, including genes related to proliferation, apoptosis, genome stability, chromatin regulation, immune evasion, RNA processing and protein homeostasis. Down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies. We estimate that near-saturation may be achieved with 600–5,000 samples per tumour type, depending on background mutation frequency. The results may help to guide the next stage of cancer genomics.

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