title: Hot spot mutations in Finnish non-small cell lung cancers.
abstract: Non-small cell lung cancer (NSCLC) is a common cancer with a poor prognosis. The aim of this study was to screen Finnish NSCLC tumor samples for common cancer-related mutations by targeted next generation sequencing and to determine their concurrences and associations with clinical features.
  
  
  
  Sequencing libraries were prepared from DNA isolated from formalin-fixed, paraffin-embedded tumor material of 425 patients using the AmpliSeq Colon and Lung panel covering mutational hot spot regions of 22 cancer genes. Sequencing was performed with the Ion Torrent Personal Genome Machine (PGM).
  
  
  
  Data analysis of the hot spot mutations revealed mutations in 77% of the patients, with 7% having 3 or more mutations reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. Two of the most frequently mutated genes were TP53 (46%) and KRAS (25%). KRAS codon 12 mutations were the most recurrently occurring mutations. EGFR mutations were significantly associated with adenocarcinoma, female gender and never/light-smoking history; CTNNB1 mutations with light ex-smokers, PIK3CA and TP53 mutations with squamous cell carcinoma, and KRAS with adenocarcinoma. TP53 mutations were most prevalent in current smokers and ERBB2, ERBB4, PIK3CA, NRAS, NOTCH1, FBWX7, PTEN and STK11 mutations occurred exclusively in a group of ever-smokers, however the association was not statistically significant. No mutation was found that associated with asbestos exposure.
  
  
  
  Finnish NSCLC patients have a similar mutation profile as other Western patients, however with a higher frequency of BRAF mutations but a lower frequency of STK11 and ERBB2 mutations. Moreover, TP53 mutations occurred frequently with other gene mutations, most commonly with KRAS, MET, EGFR and PIK3CA mutations.
authors: University of Helsinki, Faculty of Medicine, Department of Pathology, P.O. Box 21, 00014 Helsinki, Finland. Electronic address: satu.maki-nevala@helsinki.fi.
authors: Satu
authors: S
authors: Mäki-Nevala
authors: University of Helsinki, Faculty of Medicine, Department of Pathology, P.O. Box 21, 00014 Helsinki, Finland. Electronic address: virinder.sarhadi@helsinki.fi.
authors: Virinder Kaur
authors: VK
authors: Sarhadi
authors: Helsinki University Central Hospital, HUSLAB, Department of Pathology, P.O. Box 400, 00029 Helsinki, Finland. Electronic address: mikko.ronty@helsinki.fi.
authors: Mikko
authors: M
authors: Rönty
authors: Finnish Institute of Occupational Health, P.O. Box 40, 00251 Helsinki, Finland. Electronic address: eeva.kettunen@ttl.fi.
authors: Eeva
authors: E
authors: Kettunen
authors: Finnish Institute of Occupational Health, P.O. Box 40, 00251 Helsinki, Finland. Electronic address: kirsti.husgafvel-pursiainen@ttl.fi.
authors: Kirsti
authors: K
authors: Husgafvel-Pursiainen
authors: Finnish Institute of Occupational Health, P.O. Box 40, 00251 Helsinki, Finland. Electronic address: henrik.wolff@ttl.fi.
authors: Henrik
authors: H
authors: Wolff
authors: University of Helsinki and Helsinki University Hospital, Heart and Lung Center, Department of Pulmonary Medicine, P.O. Box 340, 00029 Helsinki, Finland. Electronic address: aija.knuuttila@hus.fi.
authors: Aija
authors: A
authors: Knuuttila
authors: University of Helsinki, Faculty of Medicine, Department of Pathology, P.O. Box 21, 00014 Helsinki, Finland. Electronic address: sakari.knuutila@helsinki.fi.
authors: Sakari
authors: S
authors: Knuutila
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009857:Oncogenes; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Lung cancer; Mutation; Non-small cell lung cancer