Regional copy number–independent deregulation of transcription in cancer
Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppressio...
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| Veröffentlicht in: | Nature genetics 2006-12, Vol.38 (12), p.1386-1396 |
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| creator | Stransky, Nicolas Vallot, Céline Reyal, Fabien Bernard-Pierrot, Isabelle de Medina, Sixtina Gil Diez Segraves, Rick de Rycke, Yann Elvin, Paul Cassidy, Andrew Spraggon, Carolyn Graham, Alexander Southgate, Jennifer Asselain, Bernard Allory, Yves Abbou, Claude C Albertson, Donna G Thiery, Jean Paul Chopin, Dominique K Pinkel, Daniel Radvanyi, François |
| description | Genetic and epigenetic alterations have been identified that lead to transcriptional deregulation in cancers. Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation. |
| doi_str_mv | 10.1038/ng1923 |
| format | Article |
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Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng1923</identifier><identifier>PMID: 17099711</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Animal Genetics and Genomics ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cancer Research ; Cell Line, Tumor ; Chromosomes, Human, Pair 3 - genetics ; Deoxyribonucleic acid ; Deregulation ; DNA ; DNA Methylation ; DNA, Neoplasm - genetics ; DNA, Neoplasm - metabolism ; Epigenesis, Genetic ; Fundamental and applied biological sciences. Psychology ; Gene Dosage ; Gene expression ; Gene Expression Regulation, Neoplastic ; Gene Function ; Genetic aspects ; Genetic regulation ; Genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Health aspects ; Human Genetics ; Humans ; Molecular and cellular biology ; Molecular genetics ; Nucleotide sequence ; Oligonucleotide Array Sequence Analysis ; Physiological aspects ; Regions ; Transcription, Genetic ; Transcription. Transcription factor. Splicing. 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Genetic mechanisms may affect single genes or regions containing several neighboring genes, as has been shown for DNA copy number changes. It was recently reported that epigenetic suppression of gene expression can also extend to a whole region; this is known as long-range epigenetic silencing. Various techniques are available for identifying regional genetic alterations, but no large-scale analysis has yet been carried out to obtain an overview of regional epigenetic alterations. We carried out an exhaustive search for regions susceptible to such mechanisms using a combination of transcriptome correlation map analysis and array CGH data for a series of bladder carcinomas. We validated one candidate region experimentally, demonstrating histone methylation leading to the loss of expression of neighboring genes without DNA methylation.</description><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cell Line, Tumor</subject><subject>Chromosomes, Human, Pair 3 - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>Deregulation</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>DNA, Neoplasm - genetics</subject><subject>DNA, Neoplasm - metabolism</subject><subject>Epigenesis, Genetic</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Dosage</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Function</subject><subject>Genetic aspects</subject><subject>Genetic regulation</subject><subject>Genetics</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Nucleotide sequence</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Physiological aspects</subject><subject>Regions</subject><subject>Transcription, Genetic</subject><subject>Transcription. Transcription factor. Splicing. 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| subjects | Agriculture Animal Genetics and Genomics Biological and medical sciences Biomedical and Life Sciences Biomedicine Cancer Cancer Research Cell Line, Tumor Chromosomes, Human, Pair 3 - genetics Deoxyribonucleic acid Deregulation DNA DNA Methylation DNA, Neoplasm - genetics DNA, Neoplasm - metabolism Epigenesis, Genetic Fundamental and applied biological sciences. Psychology Gene Dosage Gene expression Gene Expression Regulation, Neoplastic Gene Function Genetic aspects Genetic regulation Genetics Genetics of eukaryotes. Biological and molecular evolution Health aspects Human Genetics Humans Molecular and cellular biology Molecular genetics Nucleotide sequence Oligonucleotide Array Sequence Analysis Physiological aspects Regions Transcription, Genetic Transcription. Transcription factor. Splicing. Rna processing Urinary Bladder Neoplasms - genetics |
| title | Regional copy number–independent deregulation of transcription in cancer |
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