Ovarian cancer mutations across populations show similarities and unique differences

An extensive tumor genomic analysis of individuals with ovarian cancer, led by researchers from Huntsman Cancer Institute at the University of Utah (the U) and Emory University, revealed that Black women have nearly identical mutations to other previously studied populations. But researchers also found a few notable differences that may be clinically relevant.

Our analysis shows the importance of researching different types of populations. The molecular features that we discover in one patient group will allow us to find potential targets for drug therapies that will work for all patients and improve ovarian cancer health care for everyone."

Jen Doherty, MS, PhD, co-principal investigator of the study and co-leader of the Cancer Control and Population Sciences Program at Huntsman Cancer Institute and professor of population health sciences at the U

Ovarian cancer is often diagnosed in its later stages due to a lack of clear symptoms or an effective screening approach, according to the National Cancer Institute. Over 12,000 women are estimated to have died from the disease in 2024. Extensive federal and private research has been devoted to understanding the causes and optimal treatment regimens for this deadly type of disease.

The study included individuals between 20 to 79 years of age who had been diagnosed with high-grade serous ovarian cancer, the most common ovarian cancer. State-of-the-art tumor sequencing technology was used to discern tumor characteristics.

Molecular epidemiologist Kayleigh Lawson-Michod, MPH, PhD, a recent graduate from the U's Population Health Sciences doctoral program, is the first author of the study.

"Prior characterizations, or analyses, of mutations in ovarian cancers were done in predominantly white populations," says Lawson-Michod. "This project was unique in that it was the first large study to characterize tumor mutations in Black individuals with high-grade serous ovarian cancer."

The team compared the results of their research to those of the Cancer Genome Atlas (TCGA), a National Cancer Institute-initiated landmark genomics database that characterized the genetic makeup of 33 cancer types. Most of the high-grade serous ovarian cancer samples analyzed in TCGA were from white individuals.

The researchers wanted to understand if there were distinctions in the tumors of certain populations given differences in survival.

"The characterizations between these groups showed similar mutations. But Black individuals have a 43% five-year overall survival rate for ovarian cancer, compared to 51% for all American women," says Doherty. "Our research shows that this discrepancy is unlikely to be explained by the genetic makeup of the tumors themselves."

Still, the research team did note a few key differences.

In the analysis of Black individuals, KRAS mutations were more prevalent than in white individuals. KRAS is a mutated gene that causes cancer.

"KRAS did not show up as a significant mutation in the high-grade serous ovarian cancer patients from TCGA," says Lawson-Michod. "However, just because KRAS may be more prevalent in Black individuals does not mean it is not present in all populations with this cancer type. If validated, this could be a missed treatment opportunity."

Researchers also noted that Black women in the study had a higher prevalence of homologous recombination deficiency (HRD). HRD prevents damaged cells from repairing themselves. HRD tumors are sensitive to PARP inhibitors, a type of targeted therapy.

"HRD status is associated with better survival, but Black women have higher mortality rates from this disease than other women," says Joellen Schildkraut, PhD, MPH, co-principal investigator of the study, member of the Cancer Prevention and Control Research Program at Winship Cancer Institute of Emory University, and professor of epidemiology at Emory University. "This characterization of ovarian cancer in an understudied population such as this can hopefully impact clinical decision-making for all women with ovarian cancer and inform targeted treatment for this disease."

The results of this study have been published in Cancer Research, a journal of the American Association for Cancer Research.

The research described in this release is supported by the National Institutes of Health/National Cancer Institute, including P30 CA042014, and Huntsman Cancer Foundation.