Comparison of gene expression and DNA copy number changes in a murine model of lung cancer

Alejandro Sweet-Cordero, George C. Tseng, Han You, Margaret Douglass, Bing Huey, Donna Albertson, Tyler Jacks

Research output: Contribution to journalArticle

Abstract

Activation of oncogenic Kras in murine lung leads to the development of numerous small adenomas, only some of which progress over time to overt adenocarcinoma. Thus, although Kras is the initiating oncogene, it is likely that secondary genetic events are required for progression from adenoma to adenocarcinoma. Some of these secondary events may also be important in human lung adenocarcinoma. By comparing gene expression profiles with DNA copy number changes, we sought to identify genes that play key roles in tumor progression in this model. Gene expression profiling revealed significant heterogeneity among the tumor samples. In 27% of the tumors analyzed, whole- or subchromosome duplications or deletions in one or more chromosomes were seen. Recurrent duplications were seen on chromosomes 6, 8, 16, and 19, whereas chromosomes 4, 11, and 17 were frequently lost. Notably, focal amplifications or deletions were not seen. Despite the lack of focal amplication, we showed that chromosome duplication has a measurable effect on gene expression that is not uniform across the genome. We identified a group of genes whose gene expression was highly correlated with changes in DNA copy number. These highly correlated genes were enriched for gene ontology categories involved in the DNA damage response and telomere maintenance.

Original languageEnglish (US)
Pages (from-to)338-348
Number of pages11
JournalGenes Chromosomes and Cancer
Volume45
Issue number4
DOIs
StatePublished - Apr 1 2006

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Comparison of gene expression and DNA copy number changes in a murine model of lung cancer'. Together they form a unique fingerprint.

  • Cite this