In a cancer genome, the noncoding sequence contains the vast majority of somatic mutations. While very few are expected to be cancer drivers, those affecting regulatory elements have the potential to have downstream effects on gene regulation that may contribute to cancer progression. To prioritize regulatory mutations, we screened somatic mutations in the Pan-Cancer Analysis of Whole Genomes cohort of 2,515 cancer genomes on individual bases to assess their potential regulatory roles in their respective cancer types. We found a highly significant enrichment of regulatory mutations associated with the deamination signature overlapping a CpG site in the CCAAT/Enhancer Binding Protein β recognition sites in many cancer types. Overall, 5,749 mutated regulatory elements were identified in 1,844 tumor samples from 39 cohorts containing 11,962 candidate regulatory mutations. Our analysis indicated 20 or more regulatory mutations in 5.5% of the samples, and an overall average of six per tumor. Several recurrent elements were identified, and major cancer-related pathways were significantly enriched for genes nearby the mutated regulatory elements. Our results provide a detailed view of the role of regulatory elements in cancer genomes.

中文翻译：

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癌症中非编码突变的功能注释。

在癌症基因组中，非编码序列包含绝大多数体细胞突变。虽然预计很少有癌症驱动因素，但那些影响调控元件的因素有可能对基因调控产生下游影响，从而可能导致癌症进展。为了优先考虑调控突变，我们在全基因组的泛癌症分析队列中筛选了个体基础上的 2,515 个癌症基因组的体细胞突变，以评估它们在各自癌症类型中的潜在调控作用。我们发现在许多癌症类型中，与 CCAAT/增强子结合蛋白 β 识别位点中的 CpG 位点重叠的脱氨标记相关的调节突变高度显着富集。总体而言，在来自 39 个包含 11 个、962 个候选调控突变。我们的分析表明，5.5% 的样本中有 20 个或更多的调节突变，每个肿瘤平均有 6 个。确定了几个复发元件，并且在突变调控元件附近的基因中显着富集了主要的癌症相关途径。我们的研究结果详细说明了调控元件在癌症基因组中的作用。