Somatic point mutation data from microsatellite unstable colorectal cancers

Microsatellite instability (MSI) leads to accumulation of an excessive number of mutations in the genome, mostly small insertions and deletions. MSI CRCs, however, also contain more point mutations than microsatellite stable (MSS) tumors, yet they have not been as comprehensively studied. To identify candidate driver genes affected by point mutations in MSI CRC, we ranked genes based on mutation significance while correcting for replication timing and gene expression utilizing an algorithm, MutSigCV. Somatic point mutation data from the exome kit-targeted area from 24 exome sequenced sporadic MSI CRCs and respective normals, and 12 whole genome sequenced sporadic MSI CRCs and respective normals were utilized. The top 73 genes were validated in 93 additional MSI CRCs.EGA study EGAS00001003101

微卫星不稳定性（Microsatellite Instability, MSI）可导致基因组内突变数量过度累积，此类突变多为小型插入与缺失变异。然而，相较于微卫星稳定型（Microsatellite Stable, MSS）肿瘤，微卫星不稳定型结直肠癌（MSI CRC）携带更多点突变，但目前针对该类肿瘤的研究仍不够全面。为筛选受微卫星不稳定型结直肠癌中点突变影响的潜在驱动基因，本研究以突变显著性为依据对基因进行排序，并通过算法MutSigCV校正了复制时间与基因表达的偏倚。本研究使用的数据包括：24例外显子组测序的散发性MSI结直肠癌及其配对正常组织的外显子组试剂盒靶向捕获区域体细胞点突变数据，以及12例全基因组测序的散发性MSI结直肠癌及其配对正常组织的体细胞点突变数据。研究人员在额外的93例MSI结直肠癌样本中对排名前73的基因开展了验证。EGA研究 EGAS00001003101