Genomics has benefited from an explosion in affordable high-throughput technology for whole-genome sequencing. The regulatory and functional aspects in non-coding regions may be an important contributor to oncogenesis. Whole-genome tumor-normal paired alignments were used to examine the non-coding regions in five cancer types and two races. Both a sliding window and a binning strategy were introduced to uncover areas of higher than expected variation for additional study. We show that the majority of cancer associated mutations in 154 whole-genome sequences covering breast invasive carcinoma, colon adenocarcinoma, kidney renal papillary cell carcinoma, lung adenocarcinoma and uterine corpus endometrial carcinoma cancers and two races are found outside of the coding region (4 432 885 in non-gene regions versus 1 412 731 in gene regions). A pan-cancer analysis found significantly mutated windows (292 to 3881 in count) demonstrating that there are significant numbers of large mutated regions in the non-coding genome. The 59 significantly mutated windows were found in all studied races and cancers. These offer 16 regions ripe for additional study within 12 different chromosomes—2, 4, 5, 7, 10, 11, 16, 18, 20, 21 and X. Many of these regions were found in centromeric locations. The X chromosome had the largest set of universal windows that cluster almost exclusively in Xq11.1—an area linked to chromosomal instability and oncogenesis. Large consecutive clusters (super windows) were found (19 to 114 in count) providing further evidence that large mutated regions in the genome are influencing cancer development. We show remarkable similarity in highly mutated non-coding regions across both cancer and race.

中文翻译：

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正常肿瘤全基因组序列样本中非编码区的扫描窗口分析。

基因组学受益于全基因组测序的经济实惠的高通量技术的爆炸式增长。非编码区的调节和功能方面可能是肿瘤发生的重要因素。全基因组肿瘤-正常配对比对用于检查五种癌症类型和两种种族的非编码区。引入了滑动窗口和分箱策略以发现高于预期变化的区域以供进一步研究。我们表明，在涵盖乳腺癌、结肠腺癌、肾肾乳头状细胞癌、肺腺癌和子宫内膜癌的 154 个全基因组序列中，大多数癌症相关突变和两个种族都在编码区之外发现（4 432在非基因区域中为 885，而在基因区域中为 1 412 731）。一项泛癌分析发现显着突变的窗口（计数为 292 到 3881）表明非编码基因组中有大量的大突变区域。在所有研究的种族和癌症中都发现了 59 个显着突变的窗口。这些在 12 条不同的染色体（2、4、5、7、10、11、16、18、20、21 和 X）中提供了 16 个成熟的区域，可供进一步研究。其中许多区域位于着丝粒位置。X 染色体拥有最大的一组通用窗口，这些窗口几乎只集中在 Xq11.1 中——这是一个与染色体不稳定性和肿瘤发生相关的区域。发现了大的连续簇（超级窗口）（计数为 19 到 114），进一步证明基因组中的大突变区域正在影响癌症的发展。