02687nas a2200337   4500008004100000245010400041210006900145300001000214490000700224520138200231653003401613653006501647653002501712653001001737653003201747653003301779653003201812653019101844100001502035700002202050700002602072700001602098700002502114700001402139700002202153700001602175700001502191700002102206700001602227856010602243       2005                        eng d00aA novel candidate region linked to development of both pheochromocytoma and head/neck paraganglioma0 anovel candidate region linked to development of both pheochromoc  a260-80 v423 aAlthough the histologic distinction between pheochromocytomas and head and neck paragangliomas is clear, little is known about the genetic differences between them. To date, various sets of genes have been found to be involved in inherited susceptibility to developing both tumor types, but the genes involved in sporadic pathogenesis are still unknown. To define new candidate regions, we performed CGH analysis on 29 pheochromocytomas and on 24 paragangliomas mainly of head and neck origin (20 of 24), which allowed us to differentiate between the two tumor types. Loss of 3q was significantly more frequent in pheochromocytomas, and loss of 1q appeared only in paragangliomas. We also found gain of 11q13 to be a significantly frequent alteration in malignant cases of both types. In addition, recurrent loss of 8p22-23 was found in 62% of pheochromocytomas (including all malignant cases) versus in 33% of paragangliomas, suggesting that this region contains candidate genes involved in the pathogenesis of this abnormality. Using FISH analysis on tissue microarrays, we confirmed genomic deletion of this region in 55% of pheochromocytomas compared to 12% of paragangliomas. Loss of 8p22-23 appears to be an important event in the sporadic development of these tumors, and additional molecular studies are necessary to identify candidate genes in this chromosomal region.10a80 and over Child Chromosomes10aAdolescent Adrenal Gland Neoplasms/*genetics Adult Aged Aged10aBiological/*genetics10aHuman10aPair 1/genetics Chromosomes10aPair 11/genetics Chromosomes10aPair 3/genetics Chromosomes10aPair 8/genetics Female Gene Deletion Head and Neck Neoplasms/*genetics Humans Male Middle Aged Nucleic Acid Hybridization Paraganglioma/*genetics Pheochromocytoma/*genetics Tumor Markers1 aCascon, A.1 aRuiz-Llorente, S.1 aRodriguez-Perales, S.1 aHonrado, E.1 aMartinez-Ramirez, A.1 aLeton, R.1 aMontero-Conde, C.1 aBenitez, J.1 aDopazo, J.1 aCigudosa, J., C.1 aRobledo, M.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1560934702881nas a2200397   4500008004100000245016800041210006900209300001200278490000700290520143600297653010101733653002201834653001001856653008301866653003301949653003301982653003302015653003202048653005102080100001602131700002102147700001502168700001602183700001602199700001602215700001602231700001802247700001602265700001402281700001302295700002102308700001502329700001702344700001602361856010602377       2005                        eng d00aA predictor based on the somatic genomic changes of the BRCA1/BRCA2 breast cancer tumors identifies the non-BRCA1/BRCA2 tumors with BRCA1 promoter hypermethylation0 apredictor based on the somatic genomic changes of the BRCA1BRCA2  a1146-530 v113 aThe genetic changes underlying in the development and progression of familial breast cancer are poorly understood. To identify a somatic genetic signature of tumor progression for each familial group, BRCA1, BRCA2, and non-BRCA1/BRCA2 (BRCAX) tumors, by high-resolution comparative genomic hybridization, we have analyzed 77 tumors previously characterized for BRCA1 and BRCA2 germ line mutations. Based on a combination of the somatic genetic changes observed at the six most different chromosomal regions and the status of the estrogen receptor, we developed using random forests a molecular classifier, which assigns to a given tumor a probability to belong either to the BRCA1 or to the BRCA2 class. Because 76.5% (26 of 34) of the BRCAX cases were classified with our predictor to the BRCA1 class with a probability of >50%, we analyzed the BRCA1 promoter region for aberrant methylation in all the BRCAX cases. We found that 15 of the 34 BRCAX analyzed tumors had hypermethylation of the BRCA1 gene. When we considered the predictor, we observed that all the cases with this epigenetic event were assigned to the BRCA1 class with a probability of >50%. Interestingly, 84.6% of the cases (11 of 13) assigned to the BRCA1 class with a probability >80% had an aberrant methylation of the BRCA1 promoter. This fact suggests that somatic BRCA1 inactivation could modify the profile of tumor progression in most of the BRCAX cases.10aBRCA1 Protein/*genetics BRCA2 Protein/*genetics Breast Neoplasms/*genetics/pathology Chromosomes10aGenetic/*genetics10aHuman10aHuman Humans Male Mutation Nucleic Acid Hybridization/methods Promoter Regions10aPair 12/genetics Chromosomes10aPair 15/genetics Chromosomes10aPair 18/genetics Chromosomes10aPair 2/genetics Chromosomes10aPair 8/genetics *DNA Methylation Female Genome1 aAlvarez, S.1 aDiaz-Uriarte, R.1 aOsorio, A.1 aBarroso, A.1 aMelchor, L.1 aPaz, M., F.1 aHonrado, E.1 aRodriguez, R.1 aUrioste, M.1 aValle, L.1 aDiez, O.1 aCigudosa, J., C.1 aDopazo, J.1 aEsteller, M.1 aBenitez, J.  uhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1570918202990nas 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=15382261