Frequent mutations in chromatin-remodelling genes in pulmonary carcinoids

Nat Commun. 2014 Mar 27:5:3518. doi: 10.1038/ncomms4518.

Abstract

Pulmonary carcinoids are rare neuroendocrine tumours of the lung. The molecular alterations underlying the pathogenesis of these tumours have not been systematically studied so far. Here we perform gene copy number analysis (n=54), genome/exome (n=44) and transcriptome (n=69) sequencing of pulmonary carcinoids and observe frequent mutations in chromatin-remodelling genes. Covalent histone modifiers and subunits of the SWI/SNF complex are mutated in 40 and 22.2% of the cases, respectively, with MEN1, PSIP1 and ARID1A being recurrently affected. In contrast to small-cell lung cancer and large-cell neuroendocrine lung tumours, TP53 and RB1 mutations are rare events, suggesting that pulmonary carcinoids are not early progenitor lesions of the highly aggressive lung neuroendocrine tumours but arise through independent cellular mechanisms. These data also suggest that inactivation of chromatin-remodelling genes is sufficient to drive transformation in pulmonary carcinoids.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Base Sequence
  • Carcinoid Tumor / genetics*
  • Carcinoid Tumor / pathology
  • Chromatin Assembly and Disassembly / genetics*
  • Chromosome Mapping
  • DNA Copy Number Variations
  • Exome / genetics
  • Female
  • Gene Dosage
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genome, Human / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Polymorphism, Single Nucleotide
  • Sequence Analysis, DNA
  • Young Adult