Solid-type poorly differentiated adenocarcinoma of the stomach: Deficiency of mismatch repair and SWI/SNF complex

研究成果: ジャーナルへの寄稿記事

抜粋

ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid-type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid-type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid-type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid-type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid-type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid-type PDAs. In the MMR-deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P =.0268, P =.0181, P =.0224, and P =.0071, respectively). In the MMR-proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P =.012). In conclusion, solid-type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated-type adenocarcinoma to solid-type PDA.

元の言語英語
ページ(範囲)1008-1019
ページ数12
ジャーナルCancer Science
111
発行部数3
DOI
出版物ステータス出版済み - 3 1 2020

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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