02990nas a2200325   4500008004100000245013600041210006900177300001100246490000700257520176100264653001602025653002602041653001002067653003402077653003402111653011302145653008802258100001702346700002102363700001602384700002502400700002702425700001502452700002102467700001402488700001502502700002502517700001602542856010602558       2004                        eng d00aGene expression analysis of chromosomal regions with gain or loss of genetic material detected by comparative genomic hybridization0 aGene expression analysis of chromosomal regions with gain or los  a353-650 v413 aComparative 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.10aChromosomes10aFluorescence Lymphoma10aHuman10aPair 13/*genetics Chromosomes10aPair 19/*genetics Chromosomes10aPair 6/*genetics Expressed Sequence Tags *Gene Dosage Gene Expression Profiling Humans In Situ Hybridization10aT-Cell/*genetics Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis1 aMelendez, B.1 aDiaz-Uriarte, R.1 aCuadros, M.1 aMartinez-Ramirez, A.1 aFernandez-Piqueras, J.1 aDopazo, A.1 aCigudosa, J., C.1 aRivas, C.1 aDopazo, J.1 aMartinez-Delgado, B.1 aBenitez, J.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1538226103136nas a2200397   4500008004100000245010000041210006900141300001200210490000800222520146400230653015401694653005901848653001301907653008901920653015002009653006702159653003702226653008702263653001102350100001502361700001902376700001402395700001502409700001602424700001802440700003002458700002602488700001802514700001402532700001802546700001602564700001902580700001502599700001802614856010602632       2002                        eng d00aIdentification of genes involved in resistance to interferon-alpha in cutaneous T-cell lymphoma0 aIdentification of genes involved in resistance to interferonalph  a1825-370 v1613 aInterferon-alpha therapy has been shown to be active in the treatment of mycosis fungoides although the individual response to this therapy is unpredictable and dependent on essentially unknown factors. In an effort to better understand the molecular mechanisms of interferon-alpha resistance we have developed an interferon-alpha resistant variant from a sensitive cutaneous T-cell lymphoma cell line. We have performed expression analysis to detect genes differentially expressed between both variants using a cDNA microarray including 6386 cancer-implicated genes. The experiments showed that resistance to interferon-alpha is consistently associated with changes in the expression of a set of 39 genes, involved in signal transduction, apoptosis, transcription regulation, and cell growth. Additional studies performed confirm that STAT1 and STAT3 expression and interferon-alpha induction and activation are not altered between both variants. The gene MAL, highly overexpressed by resistant cells, was also found to be expressed by tumoral cells in a series of cutaneous T-cell lymphoma patients treated with interferon-alpha and/or photochemotherapy. MAL expression was associated with longer time to complete remission. Time-course experiments of the sensitive and resistant cells showed a differential expression of a subset of genes involved in interferon-response (1 to 4 hours), cell growth and apoptosis (24 to 48 hours.), and signal transduction.10aAntineoplastic Agents/*pharmacology/therapeutic use Carrier Proteins/biosynthesis/genetics DNA-Binding Proteins/biosynthesis/genetics Drug Resistance10aBiological Oligonucleotide Array Sequence Analysis RNA10aCultured10aCutaneous/diagnosis/drug therapy/*genetics/metabolism *Membrane Glycoproteins Models10aInterleukin-1 Reproducibility of Results STAT1 Transcription Factor STAT3 Transcription Factor Trans-Activators/biosynthesis/genetics Tumor Cells10aNeoplasm Gene Expression Profiling *Gene Expression Regulation10aNeoplasm/biosynthesis *Receptors10aNeoplastic Humans Interferon-alpha/*pharmacology/therapeutic use Kinetics Lymphoma10aT-Cell1 aTracey, L.1 aVilluendas, R.1 aOrtiz, P.1 aDopazo, A.1 aSpiteri, I.1 aLombardia, L.1 aRodriguez-Peralto, J., L.1 aFernandez-Herrera, J.1 aHernandez, A.1 aFraga, J.1 aDominguez, O.1 aHerrero, J.1 aAlonso, M., A.1 aDopazo, J.1 aPiris, M., A.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12414529