A molecular portrait of microsatellite instability across multiple cancers.
A molecular portrait of microsatellite instability across multiple cancers.
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DOI：
10.1038/ncomms15180
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发表时间：
2017-06-06
影响因子：
16.6
通讯作者：
Park PJ
中科院分区：
文献类型：
--
作者：
Cortes-Ciriano I;Lee S;Park WY;Kim TM;Park PJ
微卫星不稳定性（MSI）是指DNA错配修复受损导致的基因组中短重复序列的高度突变。虽然MSI已经研究了几十年，但现在大量的测序数据使我们能够更详细地检查MSI的分子指纹。在这里，我们分析了23种癌症类型的癌症患者的18000个外显子组和1,000个全基因组。我们的分析表明，MSI事件的频率在肿瘤类型内和肿瘤类型之间是高度可变的。我们还鉴定了DNA修复和致癌途径中反复发生MSI的基因，并发现了经常显示MSI的非编码基因座。最后，我们提出了一个高度准确的基于外显子组的MSI表型预测模型。这些结果推进了我们对MSI的基因组驱动因素和后果的理解，我们全面的肿瘤类型特异性MSI基因座目录将使基于小组的MSI测试能够识别可能从免疫治疗中受益的患者。一些具有DNA错配修复缺陷的癌症显示微卫星不稳定性。在这里，作者在外显子组和全基因组水平上分析了23种癌症类型，并确定了具有复发性微卫星不稳定性的基因座，这些基因座可用于识别将从免疫治疗中受益的患者。
Microsatellite instability (MSI) refers to the hypermutability of short repetitive sequences in the genome caused by impaired DNA mismatch repair. Although MSI has been studied for decades, large amounts of sequencing data now available allows us to examine the molecular fingerprints of MSI in greater detail. Here, we analyse ∼8,000 exomes and ∼1,000 whole genomes of cancer patients across 23 cancer types. Our analysis reveals that the frequency of MSI events is highly variable within and across tumour types. We also identify genes in DNA repair and oncogenic pathways recurrently subject to MSI and uncover non-coding loci that frequently display MSI. Finally, we propose a highly accurate exome-based predictive model for the MSI phenotype. These results advance our understanding of the genomic drivers and consequences of MSI, and our comprehensive catalogue of tumour-type-specific MSI loci will enable panel-based MSI testing to identify patients who are likely to benefit from immunotherapy. Some cancers with DNA mismatch repair deficiency display microsatellite instability. Here the authors analyse twenty three cancer types at the exome and whole-genome level, and identify loci with recurrent microsatellite instability that could be used to identify patients who would benefit from immunotherapy.