Relevance of ARID1A Mutations in Endometrial Carcinomas

Since the Cancer Genome Atlas (TCGA) project identified four distinct groups based on molecular alterations, mutation analyses have been integrated into the characterization of endometrial carcinomas (ECs). ARID1A seems to be the subunit more involved in the loss of function of the SWI/SNF complex in ECs. The aim of this study is to define the relevance of ARID1A alterations in a cohort of EC, studying the possible associations between DNA mutation (genomic level), RNA expression (transcriptomic level), and protein expression (proteomic level). A total of 50 endometrial carcinomas were characterized for ARID1A mutations (using targeted DNA next-generation sequencing-NGS), ARID1A gene expression (using RNAseq and qRT-PCR), and ARID1A protein expression (using immunohistochemistry-IHC). Moreover, we have investigated if ARID1A mutations may alter the protein structure, using the Protein Data Bank sequence. We found a good correlation between ARID1A mutations and protein immunostaining, even if we did not find statistically significant differences in the ARID1A expression levels. In conclusion, our data demonstrated that the molecular characterization of ARID1A should be associated with IHC analysis, mainly in those cases harboring novel ARID1A mutations or in those alterations with uncertain pathogenic significance.

Automated summary

This study aims to investigate the relevance of ARID1A alterations in endometrial carcinomas (ECs) by studying the associations between DNA mutation, RNA expression, and protein expression. The results show a good correlation between ARID1A mutations and protein immunostaining, suggesting the use of immunohistochemistry analysis in cases with novel ARID1A mutations or alterations of uncertain pathogenic significance.