Ovarian Cancer Genome and Molecular Experimental Sciences

Abstract

A large number of genomic studies have provided important insights into molecular pathogenesis of ovarian cancer. Ovarian cancer is divided into two types: type I and type II tumors. Type I ovarian tumors include clear cell, endometrioid, mucinous, and low-grade serous carcinomas, while type II tumors are mainly high-grade serous carcinomas. High-grade serous carcinomas are characterized by TP53 gene mutations and extensive copy number alterations. Approximately half of high-grade serous ovarian carcinomas harbor homologous recombination pathway deficiency. Clear cell carcinomas are characterized by upregulation of HNF1B and IL6 and mutations in PIK3CA and ARID1A. Alterations of HNF1B pathway, IL6 pathway, PI3K pathway, and SWI/SNF complex are influenced by copy number alterations and epigenetic regulation. Endometrioid carcinomas are divided into low-grade (G1–G2) and high-grade (G3) tumors, although some of high-grade serous carcinomas have been misclassified as high-grade endometrioid carcinomas. Low-grade endometrioid carcinomas harbor mutations in CTNNB1, PTEN, KRAS, PIK3CA, and ARID1A, while high-grade endometrioid carcinomas harbor TP53 mutations. Mucinous carcinomas exhibit ERBB2/KRAS/BRAF pathway activation by KRAS or BRAF mutations or ERBB2 amplifications. Unlike other type I tumors, half of mucinous carcinomas harbor TP53 mutations. Low-grade serous carcinomas evolve from serous borderline tumor. KRAS and BRAF mutations are common in serous borderline tumors and low-grade serous carcinomas.