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

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our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS EPIGENETIC REGULATION DURING CANCER TRANSITIONS ACROSS 11 TUMOUR TYPES Article Open access 01 November 2023

INTEGRATIVE PAN CANCER ANALYSIS REVEALS EPIGENOMIC VARIATION IN CANCER TYPE AND CELL SPECIFIC CHROMATIN DOMAINS Article Open access 03 March 2021 HERITABLE TRANSCRIPTIONAL DEFECTS FROM

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development core team _R: a Language and Environment for Statistical Computing_. (R Foundation for Statistical Computing, Vienna, 2006). Download references ACKNOWLEDGEMENTS We thank C.

Rouveirol for discussions, P. Hupé for his GLAD algorithm expertise and the Institut Curie Bioinformatics Service headed by E. Barillot for support. We also thank J. Sappa from Alex Edelman

& Associates for careful reading of the manuscript and the UCSF Cancer Center Array CGH Core for providing the BAC arrays. This article is dedicated to the memory of D. Chopin, whose

commitment to cancer research was of paramount importance for the initiation of this work. This work was supported by the CNRS, the Institut Curie, AstraZeneca, the Canceropole Ile de France

and the Ligue Nationale Contre le Cancer. N.S., C.V., F. Reyal, I.B.-P., S.G.D. de M. and F. Radvanyi are members of the Equipe Oncologie Moléculaire, labellisée par La Ligue Nationale

Contre le Cancer. N.S. was supported by a fellowship from the French Ministry of Education and Research and a fellowship from the Association pour la Recherche sur le Cancer. C.V. was

supported by a fellowship from the French Ministry of Education and Research and F. Reyal by a fellowship from the Ligue Nationale Contre le Cancer. AUTHOR INFORMATION Author notes *

Dominique K Chopin: Deceased. * Nicolas Stransky and Céline Vallot: These authors contributed equally to this work. AUTHORS AND AFFILIATIONS * UMR 144 Centre National de la Recherche

Scientifique (CNRS)/Institut Curie, Paris, 75248 Cedex 05, France Nicolas Stransky, Céline Vallot, Fabien Reyal, Isabelle Bernard-Pierrot, Sixtina Gil Diez de Medina, Jean Paul Thiery & 

François Radvanyi * EMI Institut National de la Santé et de la Recherche Médicale (INSERM) 03-37, Hôpital Henri Mondor, Créteil, 94010, Cedex, France Sixtina Gil Diez de Medina, Yves Allory,

 Claude C Abbou & Dominique K Chopin * Comprehensive Cancer Center, University of California San Francisco (UCSF), San Francisco, 94143, California, USA Rick Segraves, Donna G Albertson 

& Daniel Pinkel * Department of Biostatistics, Institut Curie, Paris, 75248 Cedex 05, France Yann de Rycke & Bernard Asselain * Cancer and Infection Research Area, AstraZeneca,

Mereside, Alderley Park, Macclesfield, SK10 4TG, Cheshire, UK Paul Elvin, Andrew Cassidy, Carolyn Spraggon & Alexander Graham * Department of Biology, Jack Birch Unit of Molecular

Carcinogenesis, University of York, Heslington, YO10 5DD, York, UK Jennifer Southgate * Department of Pathology, Hôpital Henri Mondor, Créteil, 94010, Cedex, France Yves Allory * Department

of Urology, Hôpital Henri Mondor, Créteil, 94010, Cedex, France Claude C Abbou & Dominique K Chopin * Cancer Research Institute, UCSF, San Francisco, 94143, California, USA Donna G

Albertson * Department of Translational Research, Institut Curie, Paris, 75248, Cedex 05, France Jean Paul Thiery * Institute of Molecular and Cell Biology, Proteos, 138673, Singapore Jean

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INFORMATION SUPPLEMENTARY FIG. 1 Transcriptome correlation maps of all chromosomes for the 57 bladder carcinomas. (PDF 1711 kb) SUPPLEMENTARY FIG. 2 Quantitative PCR analysis of the gene

copy number of region 3-2. (PDF 33 kb) SUPPLEMENTARY TABLE 1 Transcriptome correlation map of 57 bladder carcinomas for chromosomes 1 to X (PDF 130 kb) SUPPLEMENTARY TABLE 2 Clinical data of

the 57 bladder carcinomas. (PDF 42 kb) SUPPLEMENTARY TABLE 3 Primers for quantitative PCR, COBRA and ChIP experiments. (PDF 45 kb) SUPPLEMENTARY NOTE (PDF 42 KB) RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Stransky, N., Vallot, C., Reyal, F. _et al._ Regional copy number–independent deregulation of transcription in cancer. _Nat

Genet_ 38, 1386–1396 (2006). https://doi.org/10.1038/ng1923 Download citation * Received: 09 August 2006 * Accepted: 13 October 2006 * Published: 12 November 2006 * Issue Date: 01 December

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