1. Identification of germline cancer predisposition variants during clinical ctDNA testing.
- Author
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Stout LA, Kassem N, Hunter C, Philips S, Radovich M, and Schneider BP
- Subjects
- Adult, Aged, Biomarkers, Tumor genetics, Female, Gene Frequency, Genetic Testing, Germ-Line Mutation, Humans, Male, Middle Aged, Circulating Tumor DNA genetics, Neoplasms genetics
- Abstract
Next-generation sequencing of circulating tumor DNA (ctDNA) is a non-invasive method to guide therapy selection for cancer patients. ctDNA variant allele frequency (VAF) is commonly reported and may aid in discerning whether a variant is germline or somatic. We report on the fidelity of VAF in ctDNA as a predictor for germline variant carriage. Two patient cohorts were studied. Cohort 1 included patients with known germline variants. Cohort 2 included patients with any variant detected by the ctDNA assay with VAF of 40-60%. In cohort 1, 36 of 91 (40%) known germline variants were identified through ctDNA analysis with a VAF of 39-87.6%. In cohort 2, 111 of 160 (69%) variants identified by ctDNA analysis with a VAF between 40 and 60% were found to be germline. Therefore, variants with a VAF between 40 and 60% should induce suspicion for germline status but should not be used as a replacement for germline testing.
- Published
- 2021
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