title: Detection of somatic variants in peripheral blood lymphocytes using a next generation sequencing multigene pan cancer panel.
abstract: Next Generation Sequencing (NGS) multigene panels, which are routinely used to assess hereditary cancer risk, can detect both inherited germline variants and somatic variants in cancer-risk genes. We evaluated the frequency and distribution of likely somatic Pathogenic and Likely Pathogenic variants (PVs) detected in >220,000 individuals who underwent clinical testing with a 25-gene panel between September 2013 and March 2016. Likely somatic PVs are defined as variants with NGS read frequencies from 10% to 30%. Overall, 137 (0.06%) individuals were identified as carrying likely somatic PVs, most commonly in TP53 (73), CHEK2 (27), and ATM (20). Among this group, a second PV with a NGS read frequency consistent with a germline variant within the same gene or a different gene on the panel was detected in 21 individuals (15.3%), which is similar to the detection rate in our general testing population. Likely somatic PVs accounted for 38.8% of all PVs in TP53. In comparison, likely somatic PVs accounted for <1% of PVs in most other genes. Likely somatic PVs were more frequently identified in older individuals (p < 0.001). Additional studies are ongoing to further investigate the incidence and clinical implications of somatic variants, enabling the appropriate medical management for these patients.
authors.affiliation: Myriad Genetic Laboratories, Inc., 320 Wakara Way, Salt Lake City, UT, USA. Electronic address: bcoffee@myriad.com.
authors.forename: Bradford
authors.initials: B
authors.lastname: Coffee
authors.affiliation: Myriad Genetic Laboratories, Inc., 320 Wakara Way, Salt Lake City, UT, USA.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Cox
authors.affiliation: Myriad Genetic Laboratories, Inc., 320 Wakara Way, Salt Lake City, UT, USA.
authors.forename: John
authors.initials: J
authors.lastname: Kidd
authors.affiliation: Myriad Genetic Laboratories, Inc., 320 Wakara Way, Salt Lake City, UT, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Sizemore
authors.affiliation: Myriad Genetic Laboratories, Inc., 320 Wakara Way, Salt Lake City, UT, USA.
authors.forename: Krystal
authors.initials: K
authors.lastname: Brown
authors.affiliation: Myriad Genetic Laboratories, Inc., 320 Wakara Way, Salt Lake City, UT, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Manley
authors.affiliation: Myriad Genetic Laboratories, Inc., 320 Wakara Way, Salt Lake City, UT, USA.
authors.forename: Debora
authors.initials: D
authors.lastname: Mancini-DiNardo
mesh_terms: D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D009369:Neoplasms / Q000097:blood* / Q000235:genetics*
keywords: ATM; CHEK2; TP53; cancer; next-generation sequencing; somatic variants