De Leo Antonio, Ravegnini Gloria, Musiani Francesco, Maloberti Thais, Visani Michela, Sanza Viviana, Angelini Sabrina, Perrone Anna Myriam, De Iaco Pierandrea, Corradini Angelo Gianluca, Rosini Francesca, Grillini Marco, Santini Donatella, Ceccarelli Claudio, Zamagni Claudio, Tallini Giovanni, de Biase Dario
Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna-Molecular Diagnostic Unit, Azienda USL di Bologna, 40138 Bologna, Italy.
Division of Molecular Pathology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy.
Diagnostics (Basel). 2022 Feb 25;12(3):592. doi: 10.3390/diagnostics12030592.
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 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 mutations (using targeted DNA next-generation sequencing-NGS), gene expression (using RNAseq and qRT-PCR), and ARID1A protein expression (using immunohistochemistry-IHC). Moreover, we have investigated if mutations may alter the protein structure, using the Protein Data Bank sequence. We found a good correlation between mutations and protein immunostaining, even if we did not find statistically significant differences in the expression levels. In conclusion, our data demonstrated that the molecular characterization of should be associated with IHC analysis, mainly in those cases harboring "novel" mutations or in those alterations with "uncertain" pathogenic significance.
自从癌症基因组图谱（TCGA）项目基于分子改变鉴定出四个不同的组以来，突变分析已被纳入子宫内膜癌（EC）的特征描述中。ARID1A似乎是EC中更参与SWI/SNF复合体功能丧失的亚基。本研究的目的是确定一组EC中改变的相关性，研究DNA突变（基因组水平）、RNA表达（转录组水平）和蛋白质表达（蛋白质组水平）之间可能的关联。总共对50例子宫内膜癌进行了突变（使用靶向DNA二代测序-NGS）、基因表达（使用RNAseq和qRT-PCR）以及ARID1A蛋白表达（使用免疫组织化学-IHC）的特征分析。此外，我们使用蛋白质数据库序列研究了突变是否可能改变蛋白质结构。我们发现突变与蛋白质免疫染色之间存在良好的相关性，尽管我们在表达水平上未发现统计学上的显著差异。总之，我们的数据表明，的分子特征应与IHC分析相关联，主要是在那些携带“新的”突变或具有“不确定”致病意义的改变的病例中。
