title: Increased yield of actionable mutations using multi-gene panels to assess hereditary cancer susceptibility in an ethnically diverse clinical cohort.
abstract: This study aims to assess multi-gene panel testing in an ethnically diverse clinical cancer genetics practice. We conducted a retrospective study of individuals with a personal or family history of cancer undergoing clinically indicated multi-gene panel tests of 6-110 genes, from six commercial laboratories. The 475 patients in the study included 228 Hispanics (47.6%), 166 non-Hispanic Whites (35.4%), 55 Asians (11.6%), 19 Blacks (4.0%), and seven others (1.5%). Panel testing found that 15.6% (74/475) of patients carried deleterious mutations for a total of 79 mutations identified. This included 7.4% (35/475) of patients who had a mutation identified that would not have been tested with a gene-by-gene approach. The identification of a panel-added mutation impacted clinical management for most of cases (69%, 24/35), and genetic testing was recommended for the first degree relatives of nearly all of them (91%, 32/35). Variants of uncertain significance (VUSs) were identified in a higher proportion of tests performed in ethnic minorities. Multi-gene panel testing increases the yield of mutations detected and adds to the capability of providing individualized cancer risk assessment. VUSs represent an interpretive challenge due to less data available outside of White, non-Hispanic populations. Further studies are necessary to expand understanding of the implementation and utilization of panels across broad clinical settings and patient populations.
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: Charite.Ricker@med.usc.edu.
authors.forename: Charité
authors.initials: C
authors.lastname: Ricker
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Julie O
authors.initials: JO
authors.lastname: Culver
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Katrina
authors.initials: K
authors.lastname: Lowstuter
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Duveen
authors.initials: D
authors.lastname: Sturgeon
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Julia D
authors.initials: JD
authors.lastname: Sturgeon
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Chanock
authors.affiliation: Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Gauderman
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: McDonnell
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Idos
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA; Department of Medicine, University of Southern California, Los Angeles, CA 90033, USA; Department of Preventive Medicine, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
mesh_terms: D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000208:ethnology* / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment
keywords: Hereditary cancer; cancer risk assessment; ethnic minorities; multi-gene panels; variants of uncertain significance