title: Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice.
abstract: BACKGROUND
  Personalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care.
  
  
  METHODS
  We developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping.
  
  
  RESULTS
  Pathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and β-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy.
  
  
  CONCLUSIONS
  Broad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston. Electronic address: lvsequist@partners.org.
authors.forename: L V
authors.initials: LV
authors.lastname: Sequist
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: R S
authors.initials: RS
authors.lastname: Heist
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: A T
authors.initials: AT
authors.lastname: Shaw
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: P
authors.initials: P
authors.lastname: Fidias
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston; The Mass General/North Shore Cancer Center, Danvers.
authors.forename: R
authors.initials: R
authors.lastname: Rosovsky
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: J S
authors.initials: JS
authors.lastname: Temel
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: I T
authors.initials: IT
authors.lastname: Lennes
authors.affiliation: Harvard Medical School, Boston; Department of Radiology.
authors.forename: S
authors.initials: S
authors.lastname: Digumarthy
authors.affiliation: Harvard Medical School, Boston.
authors.forename: B A
authors.initials: BA
authors.lastname: Waltman
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston.
authors.forename: E
authors.initials: E
authors.lastname: Bast
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston.
authors.forename: S
authors.initials: S
authors.lastname: Tammireddy
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston.
authors.forename: L
authors.initials: L
authors.lastname: Morrissey
authors.affiliation: Harvard Medical School, Boston; Department of Biostatistics.
authors.forename: A
authors.initials: A
authors.lastname: Muzikansky
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: S B
authors.initials: SB
authors.lastname: Goldberg
authors.affiliation: Harvard Medical School, Boston; Department of Medicine.
authors.forename: J
authors.initials: J
authors.lastname: Gainor
authors.affiliation: Harvard Medical School, Boston; Division of Pulmonary and Critical Care Medicine.
authors.forename: C L
authors.initials: CL
authors.lastname: Channick
authors.affiliation: Harvard Medical School, Boston; Division of Thoracic Surgery.
authors.forename: J C
authors.initials: JC
authors.lastname: Wain
authors.affiliation: Harvard Medical School, Boston; Division of Thoracic Surgery.
authors.forename: H
authors.initials: H
authors.lastname: Gaissert
authors.affiliation: Harvard Medical School, Boston; Division of Thoracic Surgery.
authors.forename: D M
authors.initials: DM
authors.lastname: Donahue
authors.affiliation: Harvard Medical School, Boston; Division of Thoracic Surgery.
authors.forename: A
authors.initials: A
authors.lastname: Muniappan
authors.affiliation: Harvard Medical School, Boston; Division of Thoracic Surgery.
authors.forename: C
authors.initials: C
authors.lastname: Wright
authors.affiliation: Harvard Medical School, Boston; Department of Radiation Oncology, Massachusetts General Hospital, Boston.
authors.forename: H
authors.initials: H
authors.lastname: Willers
authors.affiliation: Harvard Medical School, Boston; Division of Thoracic Surgery.
authors.forename: D J
authors.initials: DJ
authors.lastname: Mathisen
authors.affiliation: Harvard Medical School, Boston; Department of Radiation Oncology, Massachusetts General Hospital, Boston.
authors.forename: N C
authors.initials: NC
authors.lastname: Choi
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: J
authors.initials: J
authors.lastname: Baselga
authors.affiliation: Yale University School of Medicine and Yale Cancer Center, New Haven.
authors.forename: T J
authors.initials: TJ
authors.lastname: Lynch
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: L W
authors.initials: LW
authors.lastname: Ellisen
authors.affiliation: Harvard Medical School, Boston; Department of Pathology, Massachusetts General Hospital, Boston, USA.
authors.forename: M
authors.initials: M
authors.lastname: Mino-Kenudson
authors.affiliation: Harvard Medical School, Boston; Division of Thoracic Surgery.
authors.forename: M
authors.initials: M
authors.lastname: Lanuti
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: D R
authors.initials: DR
authors.lastname: Borger
authors.affiliation: Harvard Medical School, Boston; Department of Pathology, Massachusetts General Hospital, Boston, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Iafrate
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston; Harvard Medical School, Boston.
authors.forename: J A
authors.initials: JA
authors.lastname: Engelman
authors.affiliation: Harvard Medical School, Boston; Department of Pathology, Massachusetts General Hospital, Boston, USA.
authors.forename: D
authors.initials: D
authors.lastname: Dias-Santagata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002986:Clinical Trials as Topic; D003955:Diagnostic Tests, Routine; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D060885:Multiplex Polymerase Chain Reaction; D009154:Mutation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
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