Somatic mutations in two genes ID'd in stomach cancer
Somatic Mutations in Two Genes ID'd in Stomach Cancer
(HealthDay News) -- Somatic mutations have been identified in two genes, FAT4 and ARID1A, involved in cell adhesion and chromatin remodeling in some patients with stomach cancer, according to a study published online April 8 in Nature Genetics.
To investigate the somatic alterations in gastric cancer, Zhi Jiang Zang, M.B.B.S., Ph.D., from the National Cancer Centre in Singapore, and colleagues sequenced the exomes of 15 gastric adenocarcinomas and their corresponding normal DNA.
The researchers identified 718 non-silent somatic point mutations in 661 genes. TP53, PIK3CA, and ARID1A were frequently mutated in adenocarcinomas (mutated in 11, three, and three adenocarcinoma exomes, respectively). The biological pathway most enriched among the frequently mutated genes was cell adhesion. In a cadherin family gene, FAT4, prevalence screening confirmed mutations in 5 percent and genomic deletions in 4 percent of gastric tumors. In 47 percent of gastric cancers, frequent mutations were seen in chromatin remodeling genes (MLL3, MLL, and ARID1A). ARID1A mutations were detected in 8 percent of tumors, and were linked with concomitant PIK3CA mutations and microsatellite instability. Both FAT4 and ARID1A were found to exert tumor-suppressor activity in functional assays.
"Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers," Zang and colleagues conclude.