Regional copy number-independent deregulation of transcription in cancer

Nicolas Stransky, Céline Vallot, Fabien Reyal, Isabelle Bernard-Pierrot, Sixtina Gil Diez De Medina, Rick Segraves, Yann De Rycke, Paul Elvin, Andrew Cassidy, Carolyn Spraggon, Alexander Graham, Jennifer Southgate, Bernard Asselain, Yves Allory, Claude C. Abbou, Donna G. Albertson, Jean Paul Thiery, Dominique K. Chopin, Daniel Pinkel, François Radvanyi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1386-1396
Number of pages11
JournalNature Genetics
Volume38
Issue number12
DOIs
StatePublished - Dec 5 2006

ASJC Scopus subject areas

  • Genetics

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