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

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 instabi...

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Autores principales: Huang, Shih-Chiang, Ng, Kwai-Fong, Chang, Ian Yi-Feng, Chang, Chee-Jen, Chao, Yi-Chun, Chang, Shu-Chen, Chen, Min-Chi, Yeh, Ta-Sen, Chen, Tse-Ching
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822341/
https://www.ncbi.nlm.nih.gov/pubmed/33481850
http://dx.doi.org/10.1371/journal.pone.0245356
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author Huang, Shih-Chiang
Ng, Kwai-Fong
Chang, Ian Yi-Feng
Chang, Chee-Jen
Chao, Yi-Chun
Chang, Shu-Chen
Chen, Min-Chi
Yeh, Ta-Sen
Chen, Tse-Ching
author_facet Huang, Shih-Chiang
Ng, Kwai-Fong
Chang, Ian Yi-Feng
Chang, Chee-Jen
Chao, Yi-Chun
Chang, Shu-Chen
Chen, Min-Chi
Yeh, Ta-Sen
Chen, Tse-Ching
author_sort Huang, Shih-Chiang
collection PubMed
description 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.
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spelling pubmed-78223412021-01-29 The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes Huang, Shih-Chiang Ng, Kwai-Fong Chang, Ian Yi-Feng Chang, Chee-Jen Chao, Yi-Chun Chang, Shu-Chen Chen, Min-Chi Yeh, Ta-Sen Chen, Tse-Ching PLoS One Research Article 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. Public Library of Science 2021-01-22 /pmc/articles/PMC7822341/ /pubmed/33481850 http://dx.doi.org/10.1371/journal.pone.0245356 Text en © 2021 Huang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Huang, Shih-Chiang
Ng, Kwai-Fong
Chang, Ian Yi-Feng
Chang, Chee-Jen
Chao, Yi-Chun
Chang, Shu-Chen
Chen, Min-Chi
Yeh, Ta-Sen
Chen, Tse-Ching
The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes
title The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes
title_full The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes
title_fullStr The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes
title_full_unstemmed The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes
title_short The clinicopathological significance of SWI/SNF alterations in gastric cancer is associated with the molecular subtypes
title_sort clinicopathological significance of swi/snf alterations in gastric cancer is associated with the molecular subtypes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822341/
https://www.ncbi.nlm.nih.gov/pubmed/33481850
http://dx.doi.org/10.1371/journal.pone.0245356
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