Gene expression analysis of chromosomal regions with gain or loss of genetic material detected by comparative genomic hybridization.
Comparative genomic hybridization (CGH) has been widely used to detect copy number alterations in cancer and to identify regions containing candidate tumor-responsible genes; however, gene expression changes have been described only in highly amplified regions (amplicons). To study the overall impact of slight copy number changes on gene expression, we analyzed 16 T-cell lymphomas by using CGH and a custom-designed cDNA microarray containing 7,657 genes and expressed sequence tags related to tumorigenesis. We evaluated mean gene expression and variability within CGH-altered regions and explored the relationship between the effects of the gene and its position within these regions. Minimally overlapping CGH candidate areas (6q25, 13q21-q22, and 19q13.1) revealed a weak relationship between altered genomic content and gene expression. However, some candidate genes showed modified expression within these regions in the majority of tumors; these candidate genes were evaluated and confirmed in another independent series of 23 T-cell lymphomas by use of the same cDNA microarray and by FISH on a tissue microarray. When all the CGH regions detected for each tumor were considered, we found a significant increase or decrease in the mean expression of the genes contained in gained or lost regions, respectively. In addition, we found that the expression of a gene was dependent not only on its position within an altered region but also on its own mechanism of regulation: genes in the same altered region responded very differently to the gain or loss of genetic material. Supplementary material for this article can be found on the Genes, Chromosomes, and Cancer website at http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html.
Meléndez
Bárbara
B
Department of Human Genetics, Spanish National Cancer Centre (CNIO), c/ Melchor Fernández Almagro 3, 28029 Madrid, Spain.
Díaz-Uriarte
Ramón
R
Cuadros
Marta
M
Martínez-Ramírez
Angel
A
Fernández-Piqueras
José
J
Dopazo
Ana
A
Cigudosa
Juan-Cruz
JC
Rivas
Carmen
C
Dopazo
Joaquín
J
Martínez-Delgado
Beatriz
B
Benítez
Javier
J
D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D020224:Expressed Sequence Tags; D018628:Gene Dosage; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016399:Lymphoma, T-Cell / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis