Genomic Landscapes of Endometrioid and Mucinous Ovarian Cancers and Morphologically Similar Tumor Types

Endometrioid and mucinous ovarian carcinomas represent nearly a fifth of ovarian cancers, but their molecular characteristics and pathologic origins are poorly understood. To identify the genomic and epigenomic alterations characteristic of these ovarian cancer subtypes and evaluate links to morphologically similar tumors from other sites, we performed a combination of sequence, copy number, mutation signature, and rearrangement analyses from tumor samples and matched normal tissues of 133 patients, as well as methylation analyses of these tumors and tissues of 150 patients from The Cancer Genome Atlas. Genomic analyses included samples from patients with ovarian endometrioid (n = 44), ovarian mucinous (n = 43), uterine endometrioid (n = 15), and gastrointestinal mucinous carcinomas (n = 31), including mucinous carcinomas of the stomach, colon, and pancreas. In addition to identifying genes previously known to be involved in these tumors, we identified alterations in RAD51C, NOTCH4, SMARCA1/4, and JAK1 in ovarian endometrioid, ESR1 in uterine endometrioid, and SMARCA4 in ovarian mucinous carcinomas. Whole-genome sequencing revealed rearrangements involving PTEN, NF1, and NF2 in ovarian endometrioid carcinomas and NF1 and MED1 in ovarian mucinous carcinomas. The number of alterations, affected genes, and genome-wide methylation profiles were not distinguishable between ovarian and uterine endometrioid carcinomas, supporting the hypothesis that these tumors share a tissue of origin. In contrast, mutation and methylation patterns in ovarian mucinous carcinomas were different from gastrointestinal mucinous carcinomas. These analyses provide insights into the genomic landscapes and origins of mucinous and endometrioid ovarian carcinomas, providing new avenues for early clinical intervention and management of patients with these cancers.