New study findings not only reveal where the most common ovarian cancer subtype originates in certain patients, but also point to the future possibility of being able to predict who will get the disease.
The research, published in Cell Reports, was led by Clive N. Svendsen, PhD, of Cedars-Sinai Medical Center and OCRA’s Scientific Advisory Committee member Beth Y. Karlan, MD, now of UCLA Jonsson Comprehensive Cancer Center and David Geffen School of Medicine at UCLA. OCRA grantee Nur Yucer, PhD, project scientist in Dr. Svendsen’s lab, is first author of the study.
The team focused specifically on high-grade serous cancer (HGSC), also known as high-grade serous ovarian cancer (HGSOC). It is the most prevalent subtype of ovarian cancer, accounting for more than 70% of epithelial ovarian cancers. This subtype is also associated with BRCA1 and BRCA2 genetic mutations, which are inherited changes to the genes on chromosomes 17 and 13, respectively. These mutations greatly increase the risk of developing ovarian cancer, particularly in the case of BRCA1. It is estimated that more than 40% of women who have a BRCA1 mutation will develop ovarian cancer by the age of 80, which marks a significant increase from the 1.3% risk of this disease in the general population.
In order to study how ovarian cancer develops in some individuals who inherit the BRCA1 mutation, the scientists replicated one set of fallopian tube tissues using blood samples from young women who had been diagnosed with ovarian cancer and carry the BRCA1 mutation. They also developed another set of these three-dimensional models using blood samples from healthy women to use as a control. Each model, known as an organoid, mirrors the actual fallopian tube lining of the individual who provided the blood sample because it carries the same genes.
“We were surprised to find multiple cellular pathologies consistent with cancer development only in the organoids from the BRCA1 patients,” said Dr. Yucer. “Organoids derived from women with the most aggressive ovarian cancer displayed the most severe organoid pathology.”
Their learnings support findings from other recent studies that many cases of HGSC actually originate in the epithelium or cells lining the inside of the fallopian tubes. It was previously widely believed in the scientific community that ovarian cancers develop in the epithelial cells covering the exterior surface of the ovaries.
“Our data supports recent research indicating that ovarian cancer in these patients actually begins with cancerous lesions in the fallopian tube linings,” said Dr. Svendsen. “If we can detect these abnormalities at the outset, we may be able to short-circuit the ovarian cancer.”
These findings may pave the way for physicians to predict which individuals who carry a BRCA mutation are most likely to develop ovarian cancer — even decades in advance. And since these organoids or models that can be created are “twins” of an individual’s actual fallopian tubes, they could also potentially be used to test how well a drug would work on a patient without having to expose that person to the treatment.
Read more in Cell Reports.
More on genetic mutations and HGSC:
- Researchers Identify Antibiotic Found to Kill Tumor Cells Containing BRCA Mutations
- Study Finds Germline Ovarian Cancer Mutations Occur Equally in Black and White Patients
- OCRA-Funded Research Provides a New Understanding of Ovarian Cancer Biology
- OCRA Grantees Reveal How Distinct Mutational Processes May Affect HGSOC Tumor Growth