title: Genetic mutation screen in early non--small-cell lung cancer (NSCLC) specimens.
abstract: BACKGROUND
  Testing for genetic abnormalities in epithelial growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and potentially additional genes is a critical tool in the care of advanced NSCLC. There is conflicting evidence for the role of such tests in early NSCLC. We report a single-institute Sequenom testing for a wide range of mutations and their clinical correlations in early-resected NSCLC specimens.
  
  
  METHODS
  Early NSCLC paraffin-embedded, formalin-fixed (FFPE) specimens were collected, DNA extracted, and using Sequenom-based matrix-assisted laser desorption/ionization-time of flight analysis, mutations in 22 oncogenes and tumor suppressor genes were evaluated. Clinical data was collected retrospectively.
  
  
  RESULTS
  The technique was found to be feasible. Thirty-six of 96 patients (37.5%) had any genetic abnormality identified, and 8 (8.3%) had 2 or more mutations. Kirsten rat sarcoma viral oncogene homolog (KRAS) and EGFR were the most common genes to appear mutated (15.6%); phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) was the gene to be found most commonly in tumors with co-mutations. Transversions were found mostly in KRAS gene mutations and to be nonprognostic. No difference in the spectrum of mutations was found between squamous-cell and non-squamous-cell lung cancers. Ever-smokers showed a trend for worse prognosis, with a similar spectrum of mutations.
  
  
  CONCLUSIONS
  Sequenom-based mutation screen is feasible using FFPE samples. More than a third of the patients were found to harbor some genetic abnormality, and 8% were found to have more than a single mutated gene. Wide-range gene screens using large sample depositories are required for further insight into the important genes at play in early NSCLC.
authors.affiliation: Institute of Oncology, Sheba Medical Center, Tel-Hashomer, Israel; Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel. Electronic address: bar.jair@gmail.com.
authors.forename: Jair
authors.initials: J
authors.lastname: Bar
authors.affiliation: Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Damianovich
authors.affiliation: Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Goni
authors.initials: G
authors.lastname: Hout Siloni
authors.affiliation: Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Erel
authors.initials: E
authors.lastname: Dar
authors.affiliation: Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Cohen
authors.affiliation: Institute of Pathology, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Marina
authors.initials: M
authors.lastname: Perelman
authors.affiliation: Thoracic Surgery, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Ben Nun
authors.affiliation: Thoracic Surgery, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Simansky
authors.affiliation: Thoracic Surgery, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Alon
authors.initials: A
authors.lastname: Yellin
authors.affiliation: Peter MacCallum Cancer Center, East Melbourne, Victoria, Australia.
authors.forename: Damien
authors.initials: D
authors.lastname: Urban
authors.affiliation: Institute of Oncology, Sheba Medical Center, Tel-Hashomer, Israel; Cancer Research Center, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Amir
authors.initials: A
authors.lastname: Onn
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000235:genetics*; D005500:Follow-Up Studies; D005820:Genetic Testing; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015996:Survival Rate
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Co-mutation; FFPE; Sequenom; Transitions; Transversion