CHA Cancer Institute, CHA University, Seoul 135-081, Korea.
Genome Res. 2013 Jul;23(7):1109-17. doi: 10.1101/gr.145706.112. Epub 2013 Jun 4.
Microsatellite instability (MSI) is a critical mechanism that drives genetic aberrations in cancer. To identify the entire MS mutation, we performed the first comprehensive genome- and transcriptome-wide analyses of mutations associated with MSI in Korean gastric cancer cell lines and primary tissues. We identified 18,377 MS mutations of five or more repeat nucleotides in coding sequences and untranslated regions of genes, and discovered 139 individual genes whose expression was down-regulated in association with UTR MS mutation. In addition, we found that 90.5% of MS mutations with deletions in gene regions occurred in UTRs. This analysis emphasizes the genetic diversity of MSI-H gastric tumors and provides clues to the mechanistic basis of instability in microsatellite unstable gastric cancers.
微卫星不稳定性（MSI）是驱动癌症中遗传异常的关键机制。为了鉴定整个 MS 突变，我们对韩国胃癌细胞系和原发组织中与 MSI 相关的突变进行了首次全面的基因组和转录组范围的分析。我们在基因的编码序列和非翻译区中鉴定出了 18377 个五核苷酸以上重复的 MS 突变，并发现了 139 个与 UTR MS 突变相关的表达下调的单个基因。此外，我们发现 90.5%的基因区域缺失的 MS 突变发生在 UTR 中。该分析强调了 MSI-H 胃肿瘤的遗传多样性，并为微卫星不稳定型胃癌不稳定性的机制基础提供了线索。
