Abstract POSTER-BIOL-1329: The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice

The tumor suppressor p53 is the most frequently mutated gene in high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer. It remains unknown, however, whether p53 mutation can cause HGSC. To address this, we have incorporated a p53 activating mutation, p53R172H, into conditional Dicer-Pten double-knockout (DKO) mice, generating triple-mutant (TKO) mice. Like DKO mice, TKO mice develop metastatic HGSCs originating from the fallopian tube. Besides, even when fallopian tubes are removed in TKO mice, ovaries alone can spur their own metastatic HGSCs, indicating that p53 mutation can drive HGSC arising from the ovary. To further confirm the ability of p53 mutation to induce ovarian HGSC, we have generated p53^R172H-Pten double-mutant (DMu) mice, one genetic control line for TKO mice. As anticipated, these DMu mice develop metastatic HGSCs from the ovary, which spread to the abdominal cavity before killing the mice, just like fallopian tube-deficient TKO mice. Our study therefore shows that the ovary, as well as the fallopian tube, can be a source of high-grade serous ovarian cancer.

(Grant support: Marsha Rivkin Ovarian Cancer Challenge Grant; Ovarian Cancer Research Fund (OCRF); F32 NCI National Research Service Award (NRSA); and K99/R00 NCI Pathway to Independence Award)

Citation Format: Jaeyeon Kim, Donna M. Coffey, Lang Ma, Martin M. Matzuk. The ovary is an alternative site of origin for high-grade serous ovarian cancer in mice [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1329.