TY - JOUR
T1 - Chromosomal aberrations and gene expression profiles in non-small cell lung cancer
AU - Dehan, E.
AU - Ben-Dor, A.
AU - Liao, W.
AU - Lipson, D.
AU - Frimer, H.
AU - Rienstein, S.
AU - Simansky, D.
AU - Krupsky, M.
AU - Yaron, P.
AU - Friedman, E.
AU - Rechavi, G.
AU - Perlman, M.
AU - Aviram-Goldring, A.
AU - Izraeli, S.
AU - Bittner, M.
AU - Yakhini, Z.
AU - Kaminski, N.
N1 - Funding Information:
We gratefully acknowledge the help of M. Barrett and J. Dauber for critically reading this manuscript. Special thanks to G. Cojocaro and I. Shahar in collecting some of the data, and to Y. Barash for his effective participation in the first steps of the analysis process. The work of ED and NK was supported by the Tel Aviv Chapter of the Israeli Lung Association. The work of GR and MK was supported by Flight Attendants Medical Research Institute (FAMRI).
PY - 2007/5
Y1 - 2007/5
N2 - Alterations in genomic content and changes in gene expression levels are central characteristics of tumors and pivotal to the tumorigenic process. We analyzed 23 non-small cell lung cancer (NSCLC) tumors by array comparative genomic hybridization (array CGH). Aberrant regions identified included well-characterized chromosomal aberrations such as amplifications of 3q and 8q and deletions of 3p21.31. Less frequently identified aberrations such as amplifications of 7q22.3-31.31 and 12p11.23-13.2, and previously unidentified aberrations such as deletion of 11q12.3-13.3 were also detected. To enhance our ability to identify key acting genes residing in these regions, we combined array CGH results with gene expression profiling performed on the same tumor samples. We identified a set of genes with concordant changes in DNA copy number and expression levels, i.e. overexpressed genes located in amplified regions and underexpressed genes located in deleted regions. This set included members of the Wnt/β-catenin pathway, genes involved in DNA replication, and matrix metalloproteases (MMPs). Functional enrichment analysis of the genes both overexpressed and amplified revealed a significant enrichment for DNA replication and repair, and extracellular matrix component gene ontology annotations. We verified the changes in expressions of MCM2, MCM6, RUVBL1, MMP1, MMP12 by real-time quantitative PCR. Our results provide a high resolution map of copy number changes in non-small cell lung cancer. The joint analysis of array CGH and gene expression analysis highlights genes with concordant changes in expression and copy number that may be critical to lung cancer development and progression.
AB - Alterations in genomic content and changes in gene expression levels are central characteristics of tumors and pivotal to the tumorigenic process. We analyzed 23 non-small cell lung cancer (NSCLC) tumors by array comparative genomic hybridization (array CGH). Aberrant regions identified included well-characterized chromosomal aberrations such as amplifications of 3q and 8q and deletions of 3p21.31. Less frequently identified aberrations such as amplifications of 7q22.3-31.31 and 12p11.23-13.2, and previously unidentified aberrations such as deletion of 11q12.3-13.3 were also detected. To enhance our ability to identify key acting genes residing in these regions, we combined array CGH results with gene expression profiling performed on the same tumor samples. We identified a set of genes with concordant changes in DNA copy number and expression levels, i.e. overexpressed genes located in amplified regions and underexpressed genes located in deleted regions. This set included members of the Wnt/β-catenin pathway, genes involved in DNA replication, and matrix metalloproteases (MMPs). Functional enrichment analysis of the genes both overexpressed and amplified revealed a significant enrichment for DNA replication and repair, and extracellular matrix component gene ontology annotations. We verified the changes in expressions of MCM2, MCM6, RUVBL1, MMP1, MMP12 by real-time quantitative PCR. Our results provide a high resolution map of copy number changes in non-small cell lung cancer. The joint analysis of array CGH and gene expression analysis highlights genes with concordant changes in expression and copy number that may be critical to lung cancer development and progression.
KW - Array CGH
KW - Chromosomal aberrations
KW - Expression microarrays
KW - Expression profiling
KW - Non-small cell lung cancer
UR - http://www.scopus.com/inward/record.url?scp=34247274716&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2006.12.010
DO - 10.1016/j.lungcan.2006.12.010
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AN - SCOPUS:34247274716
SN - 0169-5002
VL - 56
SP - 175
EP - 184
JO - Lung Cancer
JF - Lung Cancer
IS - 2
ER -
