The shifting landscape of genetic alterations separating endometriosis and ovarian endometrioid carcinoma

Ovarian cancer is one of the most common cancers worldwide, and is associated with a prior diagnosis of endometriosis in several cases. Our aim was to correlate genetic and methylation profile of ovarian endometrioid ovarian cancer and endometriosis patients. We evaluated the genetic profile of 50 ovarian endometriosis and 20 ovarian endometrioid carcinoma samples using next generation sequencing technology. In addition, the DNA methylation profile was evaluated for both cohorts of patients. We observed several mutated genes that were common for both types of patients, but we also identified mutated genes that were characteristic for each group: JAK3, KRAS and RB1 for endometriosis; and ATM, BRAF, CDH1, EGFR, NRAS, RET and SMO for ovarian endometrioid cancer. Also we idenfied genes that are highly methylated only in endometriosis samples (PYCARD, RARB, RB1, IL2, CFTR, CD44 and CDH13) and MLH3 gene was methylated only in endometrioid ovarian carcinoma samples. Also, BRCA1, CADM1, PAX6 and PAH genes are mainly methylated in endometrioid ovarian carcinoma patients. We identified a correlation for the cancer group between tumor stage, copy number aberrations and the presence of metastases; more specifically, the presence of BRCA1 pathogenic variants was correlated with tumor differentiation degree, TP53 variants and copy number aberrations. This study was able to demonstrate the presence of similar pathways being altered in both endometriosis and ovarian endometrioid carcinoma, which could mean that a diagnosis of endometriosis could be an early marker for cancer diagnosis. In addition, we showed that GATA2 hypomethylation, ATM hypermethylation, CREM hypomethylation, higher tumor differentiation degree or higher tumor stage is associated with a poor prognosis in patients with ovarian endometrioid carcinoma.

Automated summary

The study found common mutated genes in patients with endometriosis and ovarian endometrioid carcinoma, as well as specific mutated genes for each group. In addition, certain genes were highly methylated in endometriosis samples, while others were methylated in ovarian endometrioid carcinoma samples. Moreover, BRCA1, CADM1, PAX6, and PAH genes were mainly methylated in patients with ovarian endometrioid carcinoma.