Large GeneDx Study Supports Multigene Panel Testing

A study of over 10,000 patients tested with a multigene hereditary cancer panel finds that the approach commonly spots hereditary cancer-linked gene variants that single gene tests might miss.

Marie Thibault

January 8, 2016

3 Min Read
Large GeneDx Study Supports Multigene Panel Testing

Marie Thibault

The jury is still out on whether multigene panels or single gene sequencing is best, but GeneDx, a genetic testing company, is making a case for the multigene approach.

The company found that in its analysis of 10,030 patients who received next-gen sequencing (NGS) multigene cancer panel testing, about half of the pathogenic variants found were in moderate-risk and recently-identified cancer genes. This is important because a single gene approach, which studies a specified gene—perhaps one of the well-known cancer genes like BRCA1 or BRCA2—would not have identified these lesser-known gene variants.

“Our experience, based on a large database of patients, demonstrates that multi-gene panels have the potential to identify pathogenic variants in genes that would not typically have been tested and most likely would have been missed. This study provides important empirical data for clinical decision-making when choosing between single genes and NGS cancer panel testing for a variety of cancers,” said Sherri Bale, PhD, FACMG, cofounder and managing director of GeneDx, in a press release.

The largest of its kind, the study, “Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing,” was published in December in Genetics in Medicine. The authors, from GeneDx, parent company BioReference Laboratories, and Columbia University Medical Center, analyzed the first 10,030 consecutive patients from the diagnostic laboratory who received multigene panel testing for hereditary cancer.

More than half of the patients tested were women with breast cancer, of whom 63.6% has not had previous BRCA1/BRCA2 genetic testing. Among other findings, the authors noted that “a significant proportion of the positive results were in genes that are not typically associated with the referring diagnosis.” This included more than 25% of colon cancer patients found to have genes outside of the well-known genes linked to colorectal cancer.

Of the positive variants found in the study, 48.2% were in moderate- or undefined-risk genes, and “the magnitude of the risk and complete cancer spectrum for variants in these genes is unclear,” the authors wrote. However, pathogenic variants for three moderate-risk and emerging genes for breast cancer—PALB2, ATM, and CHEK2—were found in relatively high percentages of women with breast cancer in the study, findings that “can have clear implications for clinical management,” the authors wrote.

In the paper’s conclusion, the authors stated that “The high frequency of positive findings in these more recently identified cancer genes underscores their potential contribution to hereditary cancer risk and evolving impact on medical management.”

While many point to the benefits of expanded testing with multigene panels, some critics and payers have discouraged broader use, saying there is not yet enough data to prove efficacy and that a limited understanding of how to interpret the results means such tests may not be clinically actionable.

The study authors acknowledge this, writing that “Not all patients or providers are comfortable dealing with uncertainty in management, and expansive gene panels including genes with currently unknown risks are not appropriate in all clinical contexts or for all patients.” 

Marie Thibault is the associate editor at MD+DI. Reach her at [email protected] and on Twitter @medtechmarie


About the Author(s)

Marie Thibault

Marie Thibault is the managing editor for Medical Device and Diagnostic Industry and Qmed. Reach her at [email protected] and on Twitter @MedTechMarie.

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