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

PLoS One. 2021 Jan 22;16(1):e0245356. doi: 10.1371/journal.pone.0245356. eCollection 2021.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • DNA Helicases / analysis*
  • DNA Helicases / genetics
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / genetics
  • Female
  • Gastrectomy
  • Humans
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mutation
  • Nuclear Proteins / analysis*
  • Nuclear Proteins / genetics
  • Prognosis
  • SMARCB1 Protein / analysis*
  • SMARCB1 Protein / genetics
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / surgery
  • Transcription Factors / analysis*
  • Transcription Factors / genetics


  • ARID1A protein, human
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Nuclear Proteins
  • SMARCA2 protein, human
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases

Grants and funding

This work was supported by grants from the Ministry of Science and Technology (108-2320-B-182A-018, 106-2320-B-182A-011-MY3 and 105-2320-B-182A-014) and the Chang Gung Memorial Hospital (CMRPG3F2073, CMRPG5J0091, CIRPG3D0153, CMRP3C1323 and CMRPG3G0553). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. All the funding or sources of support were received during this study and there was no additional external funding received for this study.