TY - JOUR
T1 - Identification of genes involved in squamous cell carcinoma of the lung using synchronized data from DNA copy number and transcript expression profiling analysis
AU - Lo, Ken C.
AU - Stein, Leighton C.
AU - Panzarella, Jenniffer A.
AU - Cowell, John Kenneth
AU - Hawthorn, Lesleyann
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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.
AB - 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.
KW - Array CGH
KW - Data overlay
KW - GO
KW - Gene expression analysis
KW - Pathway Analysis
KW - Squamous cell carcinoma
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UR - http://www.scopus.com/inward/citedby.url?scp=40249103182&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2007.08.037
DO - 10.1016/j.lungcan.2007.08.037
M3 - Article
C2 - 18029052
AN - SCOPUS:40249103182
SN - 0169-5002
VL - 59
SP - 315
EP - 331
JO - Lung Cancer
JF - Lung Cancer
IS - 3
ER -