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 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.
Stransky
Nicolas
N
UMR 144 Centre National de la Recherche Scientifique (CNRS)/Institut Curie, 75248 Paris Cedex 05, France.
Vallot
Céline
C
Reyal
Fabien
F
Bernard-Pierrot
Isabelle
I
de Medina
Sixtina Gil Diez
SG
Segraves
Rick
R
de Rycke
Yann
Y
Elvin
Paul
P
Cassidy
Andrew
A
Spraggon
Carolyn
C
Graham
Alexander
A
Southgate
Jennifer
J
Asselain
Bernard
B
Allory
Yves
Y
Abbou
Claude C
CC
Albertson
Donna G
DG
Thiery
Jean Paul
JP
Chopin
Dominique K
DK
Pinkel
Daniel
D
Radvanyi
François
F
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*
D004273:DNA, Neoplasm