Researchers Identify Molecular Origin of Mucinous Ovarian Carcinoma
Posted: Wednesday, October 9, 2019
An international study revealed that unlike other types of ovarian cancer, mucinous ovarian carcinoma seems to originate in the ovaries rather than metastasizing from other sites in the body. The study findings were published in Nature Communications.
“We still have a way to go before we have addressed this question for all types of ovarian cancers, especially the rarest forms, but in the case of [mucinous ovarian carcinoma], we have now confirmed this is not a metastatic tumor, but it develops at the ovary from an early stage,” stated Kylie L. Gorringe, PhD, of the Peter MacCallum Cancer Centre in Melbourne, Australia, in an institutional press release.
After performing whole-exome sequencing on a cohort of 255 primary mucinous ovarian carcinomas, the researchers identified copy number loss or mutation in CDKN2A (76% of cases), followed by mutations in KRAS and TP53 (both 64%), as the most frequent genetic events. Dr. Gorringe and colleagues then compared the tumor-sequencing data with The Cancer Genome Atlas Program, revealing that mucinous ovarian carcinoma was “clearly genetically distinct” from high-grade serous ovarian, endometrial, gastric, and colorectal tumors, including mucinous colorectal carcinomas and appendiceal neoplasms.
The investigators also identified a “model of progression” from a benign tumor to metastatic mucinous ovarian carcinoma. After a benign tumor is triggered by a KRAS or CDKN2A event, additional copy number alterations, including a “notable” amplicon on 9p13, are key drivers associated with increasing grade and metastatic disease progression. The majority of grade 3 mucinous ovarian carcinomas had associated benign or borderline components (86%), which is rare in high-grade serous ovarian carcinoma.
“Building on our study findings, there is a strong case to involve women with [mucinous ovarian carcinoma] in clinical trials of drugs already in development and which target solid tumors with genetic similarities to [mucinous ovarian carcinoma],” concluded Dr. Gorringe.
Disclosure: The study authors reported no conflicts of interest.