Characterizing the cancer genome in lung adenocarcinoma

Nature. 2007 Dec 6;450(7171):893-8. doi: 10.1038/nature06358. Epub 2007 Nov 4.

Abstract

Somatic alterations in cellular DNA underlie almost all human cancers. The prospect of targeted therapies and the development of high-resolution, genome-wide approaches are now spurring systematic efforts to characterize cancer genomes. Here we report a large-scale project to characterize copy-number alterations in primary lung adenocarcinomas. By analysis of a large collection of tumours (n = 371) using dense single nucleotide polymorphism arrays, we identify a total of 57 significantly recurrent events. We find that 26 of 39 autosomal chromosome arms show consistent large-scale copy-number gain or loss, of which only a handful have been linked to a specific gene. We also identify 31 recurrent focal events, including 24 amplifications and 7 homozygous deletions. Only six of these focal events are currently associated with known mutations in lung carcinomas. The most common event, amplification of chromosome 14q13.3, is found in approximately 12% of samples. On the basis of genomic and functional analyses, we identify NKX2-1 (NK2 homeobox 1, also called TITF1), which lies in the minimal 14q13.3 amplification interval and encodes a lineage-specific transcription factor, as a novel candidate proto-oncogene involved in a significant fraction of lung adenocarcinomas. More generally, our results indicate that many of the genes that are involved in lung adenocarcinoma remain to be discovered.

MeSH terms

  • Adenocarcinoma / genetics*
  • Cell Line, Tumor
  • Chromosome Deletion
  • Chromosomes, Human, Pair 14 / genetics
  • Gene Amplification / genetics
  • Genome, Human / genetics*
  • Genomics
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Loss of Heterozygosity / genetics
  • Lung Neoplasms / genetics*
  • Neoplasms / genetics*
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide / genetics
  • RNA Interference
  • Thyroid Nuclear Factor 1
  • Transcription Factors / genetics

Substances

  • Intracellular Signaling Peptides and Proteins
  • MBIP protein, human
  • NKX2-1 protein, human
  • Nuclear Proteins
  • Thyroid Nuclear Factor 1
  • Transcription Factors