Multiple-gene sequencing panels may provide benefit beyond BRCA testing alone, according to a study published online April 14 in the Journal of Clinical Oncology. This study begins to build an evidence base demonstrating that multigene panels hold enhanced clinical value, guiding interventions that can prevent incident cancer. Forty-two genes associated with cancer risk were sequenced from frozen samples from 198 patients referred for clinical BRCA 1/2 testing (from 2002 to 2012) using a customized germline-DNA sequencing panel. Fifty-seven of the women carried germline BRCA1/2 mutations, which was fully concordant with prior BRCA testing. An additional 16 pathogenic variants (five novel ones) were identified in other genes among the 141 women without BRCA mutations. Fifteen of these pathogenic variants were actionable and warranted a change in care (i.e., targeted screening). An average of 2.1 variants of unknown significance were seen across all genes. “This is a significant yield of potentially actionable results, comparable to the 5 percent to 10 percent probability threshold endorsed by guidelines and payers for BRCA1/2 and Lynch syndrome testing,” write the authors, led by Allison Kurian, from Stanford University in California. “Although further research is required to guide practice, these findings provide an early signal for the […]
Multiple-gene sequencing panels may provide benefit beyond BRCA testing alone, according to a study published online April 14 in the Journal of Clinical Oncology. This study begins to build an evidence base demonstrating that multigene panels hold enhanced clinical value, guiding interventions that can prevent incident cancer.
Forty-two genes associated with cancer risk were sequenced from frozen samples from 198 patients referred for clinical BRCA 1/2 testing (from 2002 to 2012) using a customized germline-DNA sequencing panel. Fifty-seven of the women carried germline BRCA1/2 mutations, which was fully concordant with prior BRCA testing. An additional 16 pathogenic variants (five novel ones) were identified in other genes among the 141 women without BRCA mutations. Fifteen of these pathogenic variants were actionable and warranted a change in care (i.e., targeted screening). An average of 2.1 variants of unknown significance were seen across all genes.
“This is a significant yield of potentially actionable results, comparable to the 5 percent to 10 percent probability threshold endorsed by guidelines and payers for BRCA1/2 and Lynch syndrome testing,” write the authors, led by Allison Kurian, from Stanford University in California. “Although further research is required to guide practice, these findings provide an early signal for the clinical relevance of multiple-gene sequencing in cancer-risk assessment.”
Several authors report financial ties to genetic testing company InVitae (San Francisco), which partially funded the study. For more information on trends affecting BRCA testing, please see Inside the Diagnostics Industry on page 5.
