Abstract
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A study by researchers from Memorial Sloan Kettering Cancer Center (MSK) that simultaneous sequencing of tumor DNA and normal tissue for a broad panel of cancer-related genes may detect more potentially clinically significant heritable mutations than a targeted approach based on current clinical guidelines.
The research, published in the Journal of the American Medical Association, found that more than half of inherited cancer gene mutations in people with advanced cancer were not detected using traditional methods based on family history.
“What was surprising about this study was the large number of individuals with inherited mutations who would not have been aware of the risk to their families had we not provided them with tumor-normal sequencing at time of their treatment evaluation,” said Kenneth Offit, M.D., chief of the clinical genetics service and Robert and Kate Niehaus Chair in Inherited Cancer Genomics at MSK.
The researchers analyzed DNA samples from 1,040 patients, finding that 182 (17.5%) had mutations indicating cancer susceptibility. Of these 182 patients, 101 (55%) would not have had these mutations detected using traditional guidelines based on family history, age, and tumor type.
Clinical actionability of pathogenic variants was defined by evidence of their utility in cancer prevention or their potential utility as therapeutic targets. The frequency of inherited mutations was related to case mix, stage, and founder mutations.