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

doi:10.1038/ng1923

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

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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 language	English (US)
Pages (from-to)	1386-1396
Number of pages	11
Journal	Nature Genetics
Volume	38
Issue number	12
DOIs	https://doi.org/10.1038/ng1923
State	Published - Dec 5 2006

ASJC Scopus subject areas

Genetics

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10.1038/ng1923

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Stransky, N., Vallot, C., Reyal, F., Bernard-Pierrot, I., De Medina, S. G. D., Segraves, R., De Rycke, Y., Elvin, P., Cassidy, A., Spraggon, C., Graham, A., Southgate, J., Asselain, B., Allory, Y., Abbou, C. C., Albertson, D. G., Thiery, J. P., Chopin, D. K., Pinkel, D., & Radvanyi, F. (2006). Regional copy number-independent deregulation of transcription in cancer. Nature Genetics, 38(12), 1386-1396. https://doi.org/10.1038/ng1923

Stransky, N, Vallot, C, Reyal, F, Bernard-Pierrot, I, De Medina, SGD, Segraves, R, De Rycke, Y, Elvin, P, Cassidy, A, Spraggon, C, Graham, A, Southgate, J, Asselain, B, Allory, Y, Abbou, CC, Albertson, DG, Thiery, JP, Chopin, DK, Pinkel, D & Radvanyi, F 2006, 'Regional copy number-independent deregulation of transcription in cancer', Nature Genetics, vol. 38, no. 12, pp. 1386-1396. https://doi.org/10.1038/ng1923

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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.",

author = "Nicolas Stransky and C{\'e}line Vallot and Fabien Reyal and Isabelle Bernard-Pierrot and {De Medina}, {Sixtina Gil Diez} and Rick Segraves and {De Rycke}, Yann and Paul Elvin and Andrew Cassidy and Carolyn Spraggon and Alexander Graham and Jennifer Southgate and Bernard Asselain and Yves Allory and Abbou, {Claude C.} and Albertson, {Donna G.} and Thiery, {Jean Paul} and Chopin, {Dominique K.} and Daniel Pinkel and Fran{\c c}ois Radvanyi",

note = "Funding Information: We thank C. Rouveirol for discussions, P. Hup{\'e} 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 Mol{\'e}culaire, labellis{\'e}e 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.",

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doi = "10.1038/ng1923",

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AU - Vallot, Céline

AU - Reyal, Fabien

AU - Bernard-Pierrot, Isabelle

AU - De Medina, Sixtina Gil Diez

AU - Segraves, Rick

AU - De Rycke, Yann

AU - Elvin, Paul

AU - Cassidy, Andrew

AU - Spraggon, Carolyn

AU - Graham, Alexander

AU - Southgate, Jennifer

AU - Asselain, Bernard

AU - Allory, Yves

AU - Abbou, Claude C.

AU - Albertson, Donna G.

AU - Thiery, Jean Paul

AU - Chopin, Dominique K.

AU - Pinkel, Daniel

AU - Radvanyi, François

N1 - Funding Information: 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.

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N2 - 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.

AB - 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.

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Regional copy number-independent deregulation of transcription in cancer

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