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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Tuesday, January 21, 2025
A new preclinical model of ovarian cancer may have provided surprising evidence that uterine serous cancer originally develops from the fallopian tubes, not the uterus, according to research conducted by Joe R. Delaney, PhD, of the Medical University of South Carolina Hollings Cancer Center, Charleston, and colleagues. In fact, activation of the MYC oncogene in combination with a fallopian tube promoter in this genetically engineered mouse model was sufficient to induce phenotypic hallmarks of human high-grade serous ovarian cancer and uterine serous carcinomas. The findings of this study were published in Cancer Research Communications.
“We could have generated the first mouse model to actually mimic this uterine serous carcinoma,” Dr. Delaney stated in a press release from the Hollings Cancer Center. “And we might have accidentally created it because it’s not a uterine cancer—it’s a metastatic form of ovarian cancer. Ovarian cancer, probably about 80% of the time, starts on the fallopian tube, not the ovary.”
The transgenic OvTrpMyc mouse model was developed through knock in of the genes MYC and Trp53 with an R270H mutation into the endogenous Trp53 locus using CRISPR-Cas9–mediated gene editing. No BRCA gene or homologous repair gene was altered in this model. Mice were monitored for signs of oncogenesis starting at 2 months of age, and euthanasia was performed once a tumor became larger than 1 cm. The uterine horns, fallopian tubes, and ovaries were then removed and examined using immunohistochemistry, cell culture, and transcriptome sequencing, among other methodologies.
Mice developed signs of high-grade serous ovarian cancer at 14.5 months on average, and they exhibited peritoneal metastasis and extensive copy number alterations. All mice showed signs of p53 and MYC expression along epithelial clusters and cells resembling endometrial intraepithelial carcinoma. Overall, the study demonstrated that MYC expression and p53-R270H mutation are sufficient to drive development of high-grade serous ovarian cancer using Ovgp1 promoter-driven transgene expression in this mouse model.
Disclosure: For full disclosures of the study authors, visit aacrjournals.org.
Cancer Research Communications
