Comprehensive genomic characterization of squamous cell lung cancers. Academic Article uri icon

Overview

MeSH

  • Adenocarcinoma
  • DNA Mutational Analysis
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, p16
  • Genes, p53
  • Genomics
  • Humans
  • Molecular Targeted Therapy
  • Mutation Rate
  • Phosphatidylinositol 3-Kinases
  • Signal Transduction

MeSH Major

  • Carcinoma, Squamous Cell
  • Genome, Human
  • Lung Neoplasms
  • Mutation

abstract

  • Lung squamous cell carcinoma is a common type of lung cancer, causing approximately 400,000 deaths per year worldwide. Genomic alterations in squamous cell lung cancers have not been comprehensively characterized, and no molecularly targeted agents have been specifically developed for its treatment. As part of The Cancer Genome Atlas, here we profile 178 lung squamous cell carcinomas to provide a comprehensive landscape of genomic and epigenomic alterations. We show that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour. We find statistically recurrent mutations in 11 genes, including mutation of TP53 in nearly all specimens. Previously unreported loss-of-function mutations are seen in the HLA-A class I major histocompatibility gene. Significantly altered pathways included NFE2L2 and KEAP1 in 34%, squamous differentiation genes in 44%, phosphatidylinositol-3-OH kinase pathway genes in 47%, and CDKN2A and RB1 in 72% of tumours. We identified a potential therapeutic target in most tumours, offering new avenues of investigation for the treatment of squamous cell lung cancers.

authors

publication date

  • September 27, 2012

has subject area

  • Adenocarcinoma
  • Carcinoma, Squamous Cell
  • DNA Mutational Analysis
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, p16
  • Genes, p53
  • Genome, Human
  • Genomics
  • Humans
  • Lung Neoplasms
  • Molecular Targeted Therapy
  • Mutation
  • Mutation Rate
  • Phosphatidylinositol 3-Kinases
  • Signal Transduction

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3466113

Digital Object Identifier (DOI)

  • 10.1038/nature11404

PubMed ID

  • 22960745

Additional Document Info

start page

  • 519

end page

  • 525

volume

  • 489

number

  • 7417