Identification of germline cancer predisposition variants during clinical ctDNA testing

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...

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Bibliographic Details
Published in:	Scientific reports 2021-07, Vol.11 (1), p.13624-13624, Article 13624
Main Authors:	Stout, Leigh Anne, Kassem, Nawal, Hunter, Cynthia, Philips, Santosh, Radovich, Milan, Schneider, Bryan P
Format:	Article
Language:	eng
Subjects:	Adult Aged Biomarkers, Tumor - genetics Cancer Circulating Tumor DNA - genetics DNA sequencing Female Gene Frequency Genetic Testing Genomics Germ-Line Mutation Humans Invasiveness Laboratories Male Middle Aged Mutation Neoplasms - genetics Next-generation sequencing Patients
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Summary:	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.
ISSN:	2045-2322 2045-2322