title: Use of panel tests in place of single gene tests in the cancer genetics clinic.
abstract: Improved technology has made it possible to test for mutations within multiple genes simultaneously. It is not clear when these gene 'panels' should be used in the hereditary cancer setting. These analyses were intended to guide panel testing criteria. Offering hereditary panel testing as a first and final, 'single-tier', option was explored. A 'two-tiered' approach, in which panel testing is offered reflexively following stricter criteria, was then applied to the same data. Within our cohort of 105 patients, the single-tier approach was associated with a higher mutation detection rate (6.7% vs 3.8%) and variant of uncertain significance (VUS) rate (0.94 vs 0.23 average per person) compared to a two-tiered approach. Of the VUSs also identified in other patients by another lab, 53% were classified differently between laboratories. Individuals reporting African American race had more VUSs compared to other ancestry groups (p = 0.001). The test cost for a single-tier test was 21% more than a two-tiered approach. Single-tier panel testing was associated with higher mutation and VUS rates, and there is inconsistent classification of the VUS/low penetrant genes between laboratories.
authors.affiliation: Department of Cancer Genetics, University of Texas Southwestern Medical Center's Harold Simmons Comprehensive Cancer Center, Dallas, TX, USA.|Department of Cancer Genetics, University of Texas Southwestern Medical Center's Moncrief Cancer Institute, Fort Worth, TX, USA.
authors.forename: A
authors.initials: A
authors.lastname: Yorczyk
authors.affiliation: Department of Cancer Genetics, University of Texas Southwestern Medical Center's Harold Simmons Comprehensive Cancer Center, Dallas, TX, USA.|Department of Cancer Genetics, University of Texas Southwestern Medical Center's Moncrief Cancer Institute, Fort Worth, TX, USA.
authors.forename: L S
authors.initials: LS
authors.lastname: Robinson
authors.affiliation: Department of Cancer Genetics, University of Texas Southwestern Medical Center's Harold Simmons Comprehensive Cancer Center, Dallas, TX, USA.|Department of Cancer Genetics, University of Texas Southwestern Medical Center's Moncrief Cancer Institute, Fort Worth, TX, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Ross
mesh_terms: D014408:Biomarkers, Tumor; D005260:Female; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor
keywords: hereditary cancer; next-generation sequencing; panel testing