导读：一个国际研究团队日前报告说，他们利用最新DNA（脱氧核糖核酸）测序技术，确认两个基因变异与胃癌具有较强关联。
胃癌或与两基因变异相关
一个国际研究团队日前报告说，他们利用最新DNA（脱氧核糖核酸）测序技术，确认两个基因变异与胃癌具有较强关联。
美国杜克大学等机构的研究人员分析了胃癌患者癌变组织和正常部位的组织。他们筛选1.8万个基因后在胃部癌变组织中发现了600多个此前未知的基因变异，其中两个基因FAT4、ARID1A发生变异与胃癌关联性最强。
在一些胃癌患者中，包含这两个基因的染色体片断甚至消失，这进一步表明，影响这两个基因的遗传缺陷在胃癌患者中可能比较常见。研究人员还在实验中发现，调控这两个基因的功能能影响胃癌细胞的生长。
相关研究报告已发表在《自然—遗传学》杂志网络版上。研究人员表示，这项研究的临床意义还需要更多研究加以证实。他们推测这两个基因可能与多种癌症相关。
统计数据显示，胃癌是全球第二大癌症，全球每年约有70万人死于胃癌。胃癌难以治愈，原因在于其很难被早期发现。在美国，接受治疗的胃癌患者5年生存率不超过25%。
Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes
Zhi Jiang Zang, Ioana Cutcutache, Song Ling Poon, Shen Li Zhang, John R McPherson, Manuel Salto-Tellez
Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers.
文献链接： https://www.nature.com/ng/journal/v44/n5/full/ng.2246.html
