Running large, multi-gene sequencing panels to assess cancer risk is a growing trend in medicine as the price of the technology declines and more precise approaches to cancer care gain steam. The tests are particularly common among breast and ovarian cancer patients. However, questions remain about the growing list of mutations and their suspected, but unproven association with breast and ovarian cancer risk. 

In a new study published in the American Journal of Human Genetics,a team led by researchers at the University of Pennsylvania’sAbramson Cancer Center (ACC) found that expanding the panel beyond the known breast/ovarian cancer-specific genes in these patients does not add any clinical benefit. Instead, testing for additional cancer susceptibility genes produced more questions than answers for breast and ovarian cancer patients.

Genetic panels sometimes reveal mutations in genes that are associated with an increased risk in developing cancer. BRCA 1 and BRCA 2 genes are prime examples, and those results may prompt women to opt for mastectomies and ovary removal surgery, which greatly decrease their risk of developing those cancers. However, there is not yet guidance for clinicians on how to care for patients who exhibit other types of mutations, such as those in CHEK2 and ATM.

To determine if there was a benefit to expanding the gene panel to include non-breast/ovarian cancer and even non-cancer susceptibility genes, the team, led by Katherine Nathanson, MD, a professor of Translational Medicine and Human Genetics, associate director of Population Science and Chief Oncogenomics Physician for the ACC, performed whole exome sequencing and then analyzed an 180 gene panel (including 25 breast/ovarian cancer specific-susceptibility genes, 123 other cancer-susceptibility genes, and 32 genes related to cardiovascular disease risk) in 404 individuals in 253 families with breast and/or ovarian cancer.  

This project was done in collaboration with researchers from the Mayo Clinic, Memorial Sloan Kettering Cancer Center and City of Hope as part of the SIMPLEXO (Simplifying Complex Exomes) consortium.

The study also evaluated the clinical utility of a variant classification methodology based on the American College of Medical Genetics and Genomics (ACMG) guidelines to help define mutations. These guidelines were recently published by the ACMG partly to address the inconsistencies in the classification of mutations among clinical laboratories.  However, a “real world” methodology using the guidelines in cancer susceptibility had not been well studied or reported.

Click here to view the full release.