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Genetic and epigenetic characteristics in ovarian tissues from polycystic ovary syndrome patients with irregular menstruation resemble those of ovarian cancer.


ABSTRACT: BACKGROUND:Irregular menstruation is clinically associated with an increased risk for ovarian cancer and disease-related mortality. This relationship remains poorly understood, and a mechanism explaining it has yet to be described. METHODS:Ovarian tissues from women with polycystic ovary syndrome (PCOS) and regular menstruation (n?=?10) or irregular menstruation (n?=?10) were subjected to DNA methylation sequencing, real-time PCR array, whole-exome sequencing, and bioinformatics analysis. RESULTS:We demonstrated that ovarian tissue from PCOS patients with irregular menstruation displayed global DNA hypomethylation, as well as hypomethylation at several functionally and oncologically significant regions. Furthermore, we showed that several cancer-related genes were aberrantly expressed in ovarian tissue from patients with irregular menstruation, and that their mRNA and microRNA profiles shared appreciable levels of coincidence with those from ovarian cancer tissue. We identified multiple point mutations in both the BRCA1 and MLH1 genes in patients with irregular menstruation, and predicted the potential pathogenicity of these mutations using bioinformatics analyses. CONCLUSIONS:Due to the nature of ovarian cancer, it is important to broaden our understanding of the pathogenesis and risk factors of the disease. Herein, we provide the first description of a genetic and epigenetic basis for the clinical relationship between irregular menstruation and an increased risk for ovarian cancer.

SUBMITTER: Jiao J 

PROVIDER: S-EPMC6416936 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

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