Journal Article

The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes

Chen, Min-Chi, Ng, Kwai-Fong, Huang, Shih-Chiang, Chen, Tse-Ching, Chang, Chee-Jen, Chang, Shu-Chen, Chao, Yi-Chun, Yeh, Ta-Sen, Chang, Ian Yi-Feng

2021

Overview

The clinicopathological significance of altered SWI/SNF complex has not been well evaluated in gastric cancer (GC). We examined SMARCA2, SMARCA4, SMARCB1 and ARID1A expression by immunohistochemistry in 1224 surgically resected GCs with subtyping into Epstein-Barr virus (EBV), microsatellite instability (MSI) and non-EBV/MSI Lauren histotypes. SWI/SNF mutations were investigated using the GC dataset of the TCGA Pan-Cancer Atlas. Clinicopathological association was assessed by statistical analysis. There were 427 cases (35%) of SWI/SNF-attenuated GC, including 344 SMARCA2 (28%), 28 SMARCA4 (2%), 11 SMARCB1 (1%) and 197 ARID1A (16%) cases. Simultaneous alterations of multiple subunits were observed. Compared to SWI/SNF-retained cases, SWI/SNF-attenuated GC exhibited a significant predilection to older ages, EBV and MSI genotypes, higher lymphatic invasion and less hematogenous recurrence ( P < 0.05). SWI/SNF attenuation was an independent risk factor for short overall survival ( P = 0.001, hazard ratio 1.360, 95% confidence interval 1.138–1.625). The survival impact stemmed from SMARCA2-attenuated GCs in stage III and non-EBV/MSI diffuse/mixed subtypes ( P = 0.019 and < 0.001, respectively). ARID1A-lost/heterogeneous GCs were more aggressive in the EBV genotype ( P = 0.016). SMARCB1 or SMARCA4 loss was not restricted to rhabdoid/undifferentiated carcinoma. In the TCGA dataset, 223 of 434 GCs (52%) harbored deleterious SWI/SNF mutations, including ARID1A (27%), SMARCA2 (9%), ARID2 (9%), ARID1B (8%), PBRM1 (7%), and SMARCA4 (7%). SWI/SNF-mutated GCs displayed a favorable outcome owing to the high percentage with the MSI genotype. In conclusion, SWI/SNF-altered GCs are common and the clinicopathological significance is related to the genotype.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adenocarcinoma / Adenosine triphosphatase / Automation / Biology and life sciences / Cancer / Cardiology / Chemotherapy / Classification / Computer programs / Copy number / Datasets / Development and progression / Epstein-Barr virus / Funding / Gastric cancer / Gastrointestinal cancer / Genetic aspects / Genomes / Health aspects / Hematology / Hospitals / Informatics / Intestine / Medical prognosis / Medical research / Medical schools / Medicine / Medicine and Health Sciences / Methodology / Molecular motors (Biochemistry) / Mutation / Pathology / Patients / Physiological aspects / Public health / Research facilities / Software / Statistical analysis / Statistics / Stomach cancer / Surgery / Tumors / Venn diagrams