title: Regional copy number-independent deregulation of transcription in cancer.
abstract: 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.
authors.affiliation: UMR 144 Centre National de la Recherche Scientifique (CNRS)/Institut Curie, 75248 Paris Cedex 05, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Stransky
authors.forename: Céline
authors.initials: C
authors.lastname: Vallot
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bernard-Pierrot
authors.forename: Sixtina Gil Diez
authors.initials: SG
authors.lastname: de Medina
authors.forename: Rick
authors.initials: R
authors.lastname: Segraves
authors.forename: Yann
authors.initials: Y
authors.lastname: de Rycke
authors.forename: Paul
authors.initials: P
authors.lastname: Elvin
authors.forename: Andrew
authors.initials: A
authors.lastname: Cassidy
authors.forename: Carolyn
authors.initials: C
authors.lastname: Spraggon
authors.forename: Alexander
authors.initials: A
authors.lastname: Graham
authors.forename: Jennifer
authors.initials: J
authors.lastname: Southgate
authors.forename: Bernard
authors.initials: B
authors.lastname: Asselain
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.forename: Claude C
authors.initials: CC
authors.lastname: Abbou
authors.forename: Donna G
authors.initials: DG
authors.lastname: Albertson
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Thiery
authors.forename: Dominique K
authors.initials: DK
authors.lastname: Chopin
authors.forename: Daniel
authors.initials: D
authors.lastname: Pinkel
authors.forename: François
authors.initials: F
authors.lastname: Radvanyi
mesh_terms: D045744:Cell Line, Tumor; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm