Comprehensive mutation profiling of mucinous gastric carcinoma

• DOI: 10.1002/path.4761
• Publication Date: 2016-06-17T12:49:35Z
• Authors: Hirofumi Rokutan; Fumie Hosoda; Natsuko Hama; Hiromi Nakamura; Yasushi Totoki; Eisaku Furukawa; Erika Arakawa; Shoko Ohashi; Tomoko Urushidate; Hironori Satoh; Hiroko Shimizu; Keiko Igarashi; Shinichi Yachida; Hitoshi Katai; Hirokazu Taniguchi; Masashi Fukayama; Tatsuhiro Shibata
• Keywords: ARID1A; MLH1; Nonsense mutation

Mucinous gastric carcinoma (MGC) is a unique subtype of cancer with poor survival outcome. Comprehensive molecular profiles and putative therapeutic targets MGC remain undetermined. We subjected 16 tumour-normal tissue pairs to whole-exome sequencing (WES) an expanded set 52 subsequent targeted sequencing. The latter focused on 114 genes identified by WES. Twenty-two histologically differentiated MGCs (D-MGCs) 46 undifferentiated (U-MGCs) were analysed. Chromatin modifier genes, including ARID1A (21%), MLL2 (19%), MLL3 (15%), KDM6A (7%), frequently mutated (47%) in MGC. also mutations potential target MTOR (9%), BRCA2 BRCA1 ERBB3 (6%). RHOA mutation was detected only 4% U-MGCs no D-MGCs. MYH9 recurrently (13%) MGC, all these being the U-MGC (p = 0.023). Three harboured nonsense mutations. knockdown enhanced cell migration induced intracytoplasmic mucin cellular elongation. BCOR associated improved survival. In U-MGCs, MLH1 expression status combined (TP53/BCL11B or TP53/MLL2) prognostic factors. A comparative analysis driver revealed that profile D-MGC similar intestinal-type cancer, whereas distinct entity, harbouring different mutational intestinal- diffuse-type cancers. Copyright © 2016 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.