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Gene panels may provide ‘middle ground’ for genomic sequencing
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A gene panel evaluating 42 genes accurately detected genetic abnormalities other than BRCA1 or BRCA2 mutations and encouraged patients to undergo genetic counseling and cancer screening, according to study results.
“Although whole-genome sequencing can clearly be useful under the right conditions, it may be premature to consider doing on everyone,” researcher James Ford, MD, professor of medicine and genetics and director of the Clinical Cancer Genetic Program at the Stanford University School of Medicine, said in a press release. “Gene panels offer a middle ground between sequencing just a single gene like BRCA1 that we are certain is involved in disease risk, and sequencing every gene in the genome. It’s a focused approach that should allow us to capture the most relevant information.”
James Ford
Ford and colleagues evaluated data from 198 women between 2002 and 2012 undergoing BRCA1/2 testing. Of the women, 57 harbored a BRCA1 or BRCA2 mutation.
Researchers used the 42-gene panel to evaluate blood specimens collected from the remaining 141 women. Overall, they detected 16 pathological variants — involving the ATM, BLM, CDH1, CDKN2A, MLH1, MUTYH, NBN, PRSS1 and SLX4 genes — for a prevalence of 11.4% (95% CI, 7.0-17.7).
Researchers determined 15 of these variants detected in 14 patients were clinically actionable. Most of these patients had a personal history of breast cancer (80%) and were non-Hispanic white (67%).
Researchers were able to recommend genetic counseling for 11 of these women or their families.
“An important question about the use of these gene panels is whether they can allow us to provide additional genetic guidance and screening,” researcher Allison Kurian, MD, assistant professor of medicine and health research and policy at Stanford, said in the press release. “We found that the participants were interested and willing to receive the additional information, and they were generally pleased at the results, which helped them make decisions about their clinical care.”
Six women were advised to undergo annual breast MRI, and six were advised to undergo regular gastrointestinal cancer screening. One woman who harbored the MLH1 mutation underwent a risk-reducing salpingo-oophorectomy and an early colonoscopy.
Researchers noted that the average number of variants of uncertain significance each patient carried across all genes was 2.1.
“We need to know how prevalent these cancer-associated mutations are in the general population,” Ford said. “We also need to be aware that, at least for a while, it’s very likely that every person will harbor one or more variants of uncertain significance. Is that information that a person would want to know? Is it helpful? In 10 years, this is likely to change as we learn more about the clinical significance of these changes.”
Disclosure: Researchers report leadership/consultant roles with, stock ownership in and research funding from Exact Sciences, Illumina and InVitae.
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