Identifying Gene Mutations in Patients With High-Grade Serious Ovarian Carcinoma
Posted: Wednesday, January 20, 2021
According to preclinical findings presented in Cell Reports, mutations to TP53 and PTEN genes, combined with disruptions of RB1, account for a core set of mutations with efficient transformation in patients with high-grade serious ovarian carcinoma. John C. Schimenti, PhD, of the College of Veterinary Medicine at Cornell University, Ithaca, and colleagues noted that the results of their analysis support the theory that most commonly mutated genes in this type of cancer have no effect on initiating the transformation of ovarian surface epithelium stem cells.
“In the past, you would know which genes were mutated, but you wouldn’t know what role they played,” Dr. Schimenti said in a Cornell University press release. “Now, you know which ones are important. And eventually, you could develop drugs to target the mutated genes that you know are causing the problem.”
In this study, the authors used data from the Cancer Genome Atlas Research Network to identify 20 genes known to mutate in high-grade serious ovarian cancer. They then employed CRISPR gene-editing technology to identify combinatorial disruptions of genes that transform from either ovarian surface epithelium stem cells or non-stem cells.
The authors found that nearly all (96%) of the ovarian surface epithelium stem cell colonies contained LentiCRISPRs targeting Trp53, which is consistent with human tumor samples that “almost universally” have TP53 mutations. In addition, most colonies had LentiCRISPRs targeting either RB1 or PTEN genes (74%), and almost half had LentiCRISPRs targeting both genes. The authors noted that most PTEN genes were also RB1, indicating that concurrent inactivation of the two genes “facilitates transformation.”
“We found there were various genes that would help the process along, but interestingly, there were other genes that, when mutated, actually inhibited the cancer initiation process,” Dr. Schimenti said.
Disclosures: The authors reported no conflicts of interest.
