Endometrial Carcinoma: Molecular Cytogenetics and Transcriptomic Profile

SIMPLE SUMMARY: Endometrial carcinomas (ECs), the most frequent type of uterine body cancer, are highly heterogeneous with overlapping clinical, pathological, and molecular features. This study aimed to gain insights into these cancers’ chromosomal and genomic aberration patterns as well as their gene and miRNA expression profiles, all of which are both pathogenetically and clinically important disease features. We found that chromosome 1 was the most frequently rearranged chromosome, mostly leading to gain of 1q, that the genes PTEN, PDGFRA, PIK3CA, and KIT were the most frequent pathogenic variants, and that some other genes and miRNAs of known importance in carcinogenesis and the immune response showed consistent deregulation. This study confirms that a high degree of genetic heterogeneity characterizes EC tumors but highlights the nonrandom involvement of some loci. ABSTRACT: Endometrial carcinomas (ECs) are histologically classified as endometrioid and nonendometrioid tumors, with each subgroup displaying different molecular profiles and clinical outcomes. Considerable biological and clinical heterogeneity exists within this scheme, however, reflecting its imperfection. We aimed to gather additional data that might help clarify the tumors’ pathogenesis and contribute toward a more meaningful classification scheme. In total, 33 ECs were examined for the presence of chromosomal aberrations, genomic imbalances, pathogenic variants, microsatellite instability, and expression profiles at both gene and miRNA levels. Chromosome 1 was the most frequently rearranged chromosome, showing a gain of all or part of the long arm. Pathogenic variants were found for PTEN (53%), PDGFRA (37%), PIK3CA (34%), and KIT (31%). High microsatellite instability was identified in 15 ECs. Comparing tumors and controls, we identified 23 differentially expressed genes of known importance in carcinogenesis, 15 genes involved in innate and adaptative immune responses, and altered expression of 7 miRNAs. miR-32-5p was the most upregulated. Our series showed a high degree of heterogeneity. Tumors were well-separated from controls, but there was no clear-cut separation between endometrioid and nonendometrioid ECs. Whether this means that the current phenotypic classification is of little relevance or if one still has not detected which genomic parameters to enter into correlation analyses remains unknown.