Epigenetic and genetic dispositions of ovarian carcinomas

Abstract

Ovarian clear cell carcinoma has unique clinical characteristics with slow growth and a stress-resistant phenotype that is epigenetically induced during cancer progression in an inflammatory microenvironment. We refer to this as an epigenetic disposition, which is frequently associated with unique biomolecular features including prominent alterations in methylation, microsatellite instability and ARID1A mutations. This characteristic methylation profile also affects glucose metabolism, commonly known as the Warburg effect. In contrast, high-grade ovarian serous adenocarcinoma has a genetic disposition that is accompanied by rapid growth, TP53 mutations and chromosomal instability. The concept of epigenetic and genetic dispositions is applicable to various malignancies, including gastric and colorectal cancers. These disposition classifications are based on fundamental characteristics of malignancies and may provide a new vantage point for development of individualized therapies.