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High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma

Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 2...

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Autores principales: Toujani, Saloua, Dessen, Philippe, Ithzar, Nathalie, Danglot, Gisèle, Richon, Catherine, Vassetzky, Yegor, Robert, Thomas, Lazar, Vladimir, Bosq, Jacques, Da Costa, Lydie, Pérot, Christine, Ribrag, Vincent, Patte, Catherine, Wiels, Jöelle, Bernheim, Alain
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739276/
https://www.ncbi.nlm.nih.gov/pubmed/19759907
http://dx.doi.org/10.1371/journal.pone.0007089
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author Toujani, Saloua
Dessen, Philippe
Ithzar, Nathalie
Danglot, Gisèle
Richon, Catherine
Vassetzky, Yegor
Robert, Thomas
Lazar, Vladimir
Bosq, Jacques
Da Costa, Lydie
Pérot, Christine
Ribrag, Vincent
Patte, Catherine
Wiels, Jöelle
Bernheim, Alain
author_facet Toujani, Saloua
Dessen, Philippe
Ithzar, Nathalie
Danglot, Gisèle
Richon, Catherine
Vassetzky, Yegor
Robert, Thomas
Lazar, Vladimir
Bosq, Jacques
Da Costa, Lydie
Pérot, Christine
Ribrag, Vincent
Patte, Catherine
Wiels, Jöelle
Bernheim, Alain
author_sort Toujani, Saloua
collection PubMed
description Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 27 Burkitt's lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs<2 Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase and BIRC6, an anti-apoptotic protein, possibly predisposing to some cancers. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs >2 Mb, gains were found in 1q (12/27), 13q (7/27), 7q (6/27), 8q(4/27), 2p (3/27), 11q (2/27) and 15q (2/27). Losses were found in 3p (5/27), 4p (4/27), 4q (4/27), 9p (4/27), 13q (4/27), 6p (3/27), 17p (3/27), 6q (2/27),11pterp13 (2/27) and 14q12q21.3 (2/27). Twenty one minimal critical regions (MCR), (range 0.04–71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2 and PIAS3. In the other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of these gains respectively. The 13q31.3q32.1 <89.58–96.81> MCR contained an amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 <60.96–61> MCR was the smallest gained MCR and specifically encompassed the REL oncogene which is already implicated in B cell lymphomas. The most frequently deleted MCR was 3p14.1 <60.43–60.53> that removed the fifth exon of FHIT. Further investigations which combined gene expression and functional studies are essential to understand the lymphomagenesis mechanism and for the development of more effective, targeted therapeutic strategies.
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spelling pubmed-27392762009-09-17 High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma Toujani, Saloua Dessen, Philippe Ithzar, Nathalie Danglot, Gisèle Richon, Catherine Vassetzky, Yegor Robert, Thomas Lazar, Vladimir Bosq, Jacques Da Costa, Lydie Pérot, Christine Ribrag, Vincent Patte, Catherine Wiels, Jöelle Bernheim, Alain PLoS One Research Article Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 27 Burkitt's lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs<2 Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase and BIRC6, an anti-apoptotic protein, possibly predisposing to some cancers. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs >2 Mb, gains were found in 1q (12/27), 13q (7/27), 7q (6/27), 8q(4/27), 2p (3/27), 11q (2/27) and 15q (2/27). Losses were found in 3p (5/27), 4p (4/27), 4q (4/27), 9p (4/27), 13q (4/27), 6p (3/27), 17p (3/27), 6q (2/27),11pterp13 (2/27) and 14q12q21.3 (2/27). Twenty one minimal critical regions (MCR), (range 0.04–71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2 and PIAS3. In the other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of these gains respectively. The 13q31.3q32.1 <89.58–96.81> MCR contained an amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 <60.96–61> MCR was the smallest gained MCR and specifically encompassed the REL oncogene which is already implicated in B cell lymphomas. The most frequently deleted MCR was 3p14.1 <60.43–60.53> that removed the fifth exon of FHIT. Further investigations which combined gene expression and functional studies are essential to understand the lymphomagenesis mechanism and for the development of more effective, targeted therapeutic strategies. Public Library of Science 2009-09-17 /pmc/articles/PMC2739276/ /pubmed/19759907 http://dx.doi.org/10.1371/journal.pone.0007089 Text en Toujani et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Toujani, Saloua
Dessen, Philippe
Ithzar, Nathalie
Danglot, Gisèle
Richon, Catherine
Vassetzky, Yegor
Robert, Thomas
Lazar, Vladimir
Bosq, Jacques
Da Costa, Lydie
Pérot, Christine
Ribrag, Vincent
Patte, Catherine
Wiels, Jöelle
Bernheim, Alain
High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma
title High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma
title_full High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma
title_fullStr High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma
title_full_unstemmed High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma
title_short High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma
title_sort high resolution genome-wide analysis of chromosomal alterations in burkitt's lymphoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739276/
https://www.ncbi.nlm.nih.gov/pubmed/19759907
http://dx.doi.org/10.1371/journal.pone.0007089
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