title: The Pitfalls of Companion Diagnostics: Evaluation of Discordant EGFR Mutation Results from a Clinical Laboratory and a Central Laboratory.
abstract: Accurate identification of somatic mutations in formalin-fixed, paraffin-embedded tumor tissue is required for enrollment into clinical trials for many novel targeted therapeutics, including trials requiring EGFR mutation status in non-small-cell lung carcinomas. Central clinical trial laboratories contracted to perform this analysis typically rely on US Food and Drug Administration-approved targeted assays to identify these mutations. We present two cases in which central laboratories inaccurately reported EGFR mutation status because of improper identification and isolation of tumor material and failure to accurately report assay limitations, resulting in enrollment denial. Such cases highlight the need for increased awareness by clinical trials of the limitation of these US Food and Drug Administration-approved assays and the necessity for a mechanism to reevaluate discordant results by alternative laboratory-developed procedures, including clinical next-generation sequencing.
authors.affiliation: Laboratory for Clinical Genomics and Advanced Technology, Department of Pathology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Turner
authors.affiliation: Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, New Hampshire.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Peterson
authors.affiliation: Laboratory for Clinical Genomics and Advanced Technology, Department of Pathology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire; Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, New Hampshire.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Pettus
authors.affiliation: Laboratory for Clinical Genomics and Advanced Technology, Department of Pathology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors.forename: Francine B
authors.initials: FB
authors.lastname: de Abreu
authors.affiliation: Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire; Department of Genetics, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire.
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.affiliation: Department of Hematology/Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Konstantin H
authors.initials: KH
authors.lastname: Dragnev
authors.affiliation: Laboratory for Clinical Genomics and Advanced Technology, Department of Pathology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire; Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, New Hampshire. Electronic address: gregory.j.tsongalis@hitchcock.org.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
mesh_terms: D000368:Aged; D064790:Clinical Laboratory Services / Q000592:standards; D004252:DNA Mutational Analysis / Q000379:methods / Q000592:standards*; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D005820:Genetic Testing / Q000379:methods / Q000592:standards*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007753:Laboratories / Q000592:standards; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D057285:Precision Medicine / Q000379:methods / Q000592:standards; D015203:Reproducibility of Results
chemical_list: D066246:ErbB Receptors