Relevance of ARID1A Mutations in Endometrial Carcinomas

Abstract

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 <i>ARID1A</i> 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 <i>ARID1A</i> mutations (using targeted DNA next-generation sequencing-NGS), <i>ARID1A</i> gene expression (using RNAseq and qRT-PCR), and ARID1A protein expression (using immunohistochemistry-IHC). Moreover, we have investigated if <i>ARID1A</i> mutations may alter the protein structure, using the Protein Data Bank sequence. We found a good correlation between <i>ARID1A</i> mutations and protein immunostaining, even if we did not find statistically significant differences in the <i>ARID1A</i> expression levels. In conclusion, our data demonstrated that the molecular characterization of <i>ARID1A</i> should be associated with IHC analysis, mainly in those cases harboring "novel" <i>ARID1A</i> mutations or in those alterations with "uncertain" pathogenic significance.