title: TP53 Mutation Spectrum in Smokers and Never Smoking Lung Cancer Patients.
abstract: BACKGROUND
  TP53 mutations are among the most common mutations found in lung cancers, identified as an independent prognostic factor in many types of cancers. The purpose of this study was to investigate the frequency and prognostic impact of TP53 mutations in never-smokers and in different histological subtypes of lung cancer.
  
  
  METHODS
  We analyzed tumor tissue from 394 non-small cell carcinomas including adenocarcinomas (n = 229), squamous cell carcinomas (n = 112), large cell carcinomas (n = 30), and others (n = 23) for mutations in TP53 by the use of Sanger sequencing (n = 394) and next generation sequencing (n = 100).
  
  
  RESULTS
  TP53 mutations were identified in 47.2% of the samples, with the highest frequency (65%) of mutations among squamous cell carcinomas. Among never-smokers, 36% carried a TP53 mutation, identified as a significant independent negative prognostic factor in this subgroup. For large cell carcinomas, a significantly prolonged progression free survival was found for those carrying a TP53 mutation. In addition, the frequency of frameshift mutations was doubled in squamous cell carcinomas (20.3%) compared to adenocarcinomas (9.1%).
  
  
  CONCLUSIONS
  TP53 mutation patterns differ between the histological subgroups of lung cancers, and are also influenced by smoking history. This indicates that the histological subtypes in lung cancer are genetically different, and that smoking-induced TP53 mutations may have a different biological impact than TP53 mutations occurring in never-smokers.
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital Oslo, Norway.
authors.forename: Ann R
authors.initials: AR
authors.lastname: Halvorsen
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital Oslo, Norway.
authors.forename: Laxmi
authors.initials: L
authors.lastname: Silwal-Pandit
authors.affiliation: Department of Tumour Biology, Institute for Cancer Research, Oslo University HospitalOslo, Norway; Genomics Core Facility, Department of Core Facilities, Institute for Cancer Research, Oslo University HospitalOslo, Norway.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Meza-Zepeda
authors.affiliation: Department of Tumour Biology, Institute for Cancer Research, Oslo University Hospital Oslo, Norway.
authors.forename: Daniel
authors.initials: D
authors.lastname: Vodak
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital Oslo, Norway.
authors.forename: Phuong
authors.initials: P
authors.lastname: Vu
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium Hospital Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Sagerup
authors.affiliation: Department of Tumour Biology, Institute for Cancer Research, Oslo University HospitalOslo, Norway; Department of Informatics, University of OsloOslo, Norway; Institute of Cancer Genetics and Informatics, Oslo University HospitalOslo, Norway.
authors.forename: Eivind
authors.initials: E
authors.lastname: Hovig
authors.affiliation: Department of Tumour Biology, Institute for Cancer Research, Oslo University Hospital Oslo, Norway.
authors.forename: Ola
authors.initials: O
authors.lastname: Myklebost
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium HospitalOslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of OsloOslo, Norway.
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium HospitalOslo, Norway; Department of Oncology, Oslo University Hospital - The Norwegian Radium HospitalOslo, Norway.
authors.forename: Odd T
authors.initials: OT
authors.lastname: Brustugun
authors.affiliation: Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital - The Norwegian Radium HospitalOslo, Norway; Department of Oncology, Oslo University Hospital - The Norwegian Radium HospitalOslo, Norway.
authors.forename: Åslaug
authors.initials: Å
authors.lastname: Helland
keywords: TP53; adenocarcinomas; large cell carcinomas; mutation spectrum; never-smoker; progression free survival; squamous cell carcinomas