title: Mutation Yield of a 34-Gene Solid Tumor Panel in Community-Based Tumor Samples.
abstract: Several targeted therapies have been approved for treatment of solid tumors. Identification of gene mutations that indicate response to these therapies is rapidly progressing. A 34-gene next-generation sequencing (NGS) panel, developed and validated by us, was evaluated to detect additional mutations in community-based cancer specimens initially sent to our reference laboratory for routine molecular testing.
  
  
  
  Consecutive de-identified clinical specimens (n = 121) from melanoma cases (n = 31), lung cancer cases (n = 27), colorectal cancer cases (n = 33), and breast cancer cases (n = 30) were profiled by NGS, and the results were compared with routine molecular testing.
  
  
  
  Upon initial mutation testing, 20 % (24/121) were positive. NGS detected ≥1 additional mutation not identified by routine testing in 74 % of specimens (90/121). Of the specimens with additional mutations, 16 harbored mutations in National Comprehensive Cancer Network guideline genes. These various additional mutations were in gene regions not routinely covered, in genes not routinely tested, and/or present at low allele frequencies. Moreover, NGS yielded no false negatives. Overall, NGS detected mutations in 59 % of the genes (20/34) included in the panel, 75 % of which (15/20) were detected in multiple tumor types. Mutations in TP53 were found in 51 % of tumors tested (62/121). Mutations in at least one other (non-TP53) gene present in the panel were detected in 64 % of cases (77/121).
  
  
  
  This assay provides improved breadth and sensitivity for profiling clinically relevant genes in these prevalent solid tumor types.
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA. heather.r.sanders@questdiagnostics.com.
authors.forename: Heather
authors.initials: H
authors.lastname: Sanders
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Qu
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Hairong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Barlan
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: James
authors.initials: J
authors.lastname: Prentice
authors.affiliation: Quest Diagnostics, Alameda, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Wolfson
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Beryl
authors.initials: B
authors.lastname: Crossley
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Sferruzza
authors.affiliation: Quest Diagnostics, Alameda, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Sninsky
authors.affiliation: Quest Diagnostics, Alameda, CA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Ross
authors.affiliation: Quest Diagnostics, Alameda, CA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Grupe
authors.affiliation: Quest Diagnostics, Alameda, CA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Catanese
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Feras
authors.initials: F
authors.lastname: Hantash
authors.affiliation: Department of Hematology and Oncology, Quest Diagnostics Nichols Institute, 33608 Ortega Highway, San Juan Capistrano, CA, 92675, USA.
authors.forename: Frederic
authors.initials: F
authors.lastname: Waldman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor; D001706:Biopsy; D005260:Female; D005787:Gene Frequency; D005820:Genetic Testing / Q000379:methods; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor