Identification of genes involved in squamous cell carcinoma of the lung using synchronized data from DNA copy number and transcript expression profiling analysis

Ken C. Lo, Leighton C. Stein, Jenniffer A. Panzarella, John Kenneth Cowell, Lesleyann Hawthorn

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Lung cancer is the leading cause of cancer deaths in the world and squamous cell carcinoma (SqCC) is the second most common in this group. Genomic DNA copy number alterations are fundamental genetic events in the development and progression of SqCC as well as other epithelial-derived cancers. The ability to identify tumor suppressor genes (TSGs) and oncogenes that are affected during tumor initiation and progression could facilitate the identification of novel molecular targets for therapeutic intervention and provide diagnostic biomarkers. Despite the association of many genetic alterations in lung cancer the molecular mechanisms of tumor progression remain ambiguous since often too many candidates are revealed using conventional genetic microarray analysis. To overcome this limitation, we have identified genes in SqCC which show concordant gene expression changes defined using microarray analysis with DNA copy number alterations defined by BAC-array comparative genomic hybridization (aCGH) in the same tumors. An in-house overlay algorithm was used to synchronize the data resulting from the two analyses. Although the expression levels of many genes were altered when compared to normal controls, those which correlated with copy number changes were far fewer, providing a manageable number for biological studies. We identified over 2000 genes which displayed both gene expression alterations and mapped to BACs which demonstrated a corresponding loss or gain. A further stringent statistical analysis identified minimal regions of overlap for losses or gains which displayed a coincident decrease or increase in the expression of genes mapping to those regions. Consistent gains involved 3q23-q29, 5p15.1-q11.1 and chromosomes 18 and 20, while consistent losses involved 3p26.3-p12.3, 9p24.3-q34.3, and chromosomes 17 and 19. The concordance finding between these two approaches suggests that DNA copy number alterations can directly influence gene expression patterns that impact on tumorigenesis in SqCC of the lung.

Original languageEnglish (US)
Pages (from-to)315-331
Number of pages17
JournalLung Cancer
Volume59
Issue number3
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

Gene Expression Profiling
Squamous Cell Carcinoma
Lung
DNA
Genes
Neoplasms
Microarray Analysis
Gene Expression
Lung Neoplasms
Chromosomes, Human, Pair 20
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 17
Comparative Genomic Hybridization
Chromosome Mapping
Tumor Suppressor Genes
Oncogenes
Cause of Death
Carcinogenesis
Biomarkers

Keywords

  • Array CGH
  • Data overlay
  • GO
  • Gene expression analysis
  • Pathway Analysis
  • Squamous cell carcinoma

ASJC Scopus subject areas

  • Oncology

Cite this

Identification of genes involved in squamous cell carcinoma of the lung using synchronized data from DNA copy number and transcript expression profiling analysis. / Lo, Ken C.; Stein, Leighton C.; Panzarella, Jenniffer A.; Cowell, John Kenneth; Hawthorn, Lesleyann.

In: Lung Cancer, Vol. 59, No. 3, 01.03.2008, p. 315-331.

Research output: Contribution to journalArticle

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