An international study has revealed the origin of mucinous ovarian cancer, confirming that unlike other types of ovarian cancer, this cancer arises from benign and borderline precursors at the ovaries and are not extraovarian metastases. These findings were published by Cheasley et al in Nature Communications.
The research provides new insights that could lead to a tailored treatment for mucinous ovarian cancer, which accounts for about 3% of all ovarian cancers.
“Recently, our understanding of ovarian cancer changed dramatically, and we now recognize the ovaries can act like a sponge for roaming cancer cells,” said senior study author Kylie Gorringe, PhD, of Peter MacCallum Cancer Centre. “Some cancers masquerade as ovarian cancers when, in fact, they originated in other organs, and by identifying where these cancers come from, we’ve been able to improve treatments and prevention. 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 cancer, we have now confirmed this is not a metastatic tumor but it develops at the ovary from an early stage.”
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Study Findings
Over 500 samples of mucinous ovarian cancer tumors and related tumors were sourced internationally for the study. The genetic events observed in mucinous ovarian cancer were compared with other tumors from many different tissue types—and this ultimately showed mucinous ovarian cancer as a unique cancer of the ovaries. Benign and borderline mucinous ovarian tumors were also sequenced, revealing they were genetically related to mucinous ovarian cancer in a way that indicates mucinous ovarian cancer could have evolved from these less aggressive tumors.
Additionally, key drivers of disease progression were identified, including mutations in the TP53 gene and copy number aberrations, including a notable amplicon on 9p13. The researchers also found that a high copy number aberration burden was associated with a worse prognosis in women with mucinous ovarian cancer.
The analysis also identified several potential targets for treatment, such as RNF43 (Wnt-pathway inhibitors), ERBB2 (HER2-targeted therapies), and potentially new dual RAS/RAF inhibitors targeting KRAS.
“Building on our study findings, there is a strong case to involve women with mucinous ovarian cancer in clinical trials of drugs already in development and which target solid tumors with genetic similarities to mucinous ovarian cancer,” concluded Dr. Gorringe.
Disclosure: For full disclosures of the study authors, visit nature.com.
