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Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status

BACKGROUND: Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biologic...

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Autores principales: Lavarino, Cinzia, Garcia, Idoia, Mackintosh, Carlos, Cheung, Nai-Kong V, Domenech, Gema, Ríos, José, Perez, Noelia, Rodríguez, Eva, de Torres, Carmen, Gerald, William L, Tuset, Esperanza, Acosta, Sandra, Beleta, Helena, de Álava, Enrique, Mora, Jaume
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2531130/
https://www.ncbi.nlm.nih.gov/pubmed/18700951
http://dx.doi.org/10.1186/1755-8794-1-36
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author Lavarino, Cinzia
Garcia, Idoia
Mackintosh, Carlos
Cheung, Nai-Kong V
Domenech, Gema
Ríos, José
Perez, Noelia
Rodríguez, Eva
de Torres, Carmen
Gerald, William L
Tuset, Esperanza
Acosta, Sandra
Beleta, Helena
de Álava, Enrique
Mora, Jaume
author_facet Lavarino, Cinzia
Garcia, Idoia
Mackintosh, Carlos
Cheung, Nai-Kong V
Domenech, Gema
Ríos, José
Perez, Noelia
Rodríguez, Eva
de Torres, Carmen
Gerald, William L
Tuset, Esperanza
Acosta, Sandra
Beleta, Helena
de Álava, Enrique
Mora, Jaume
author_sort Lavarino, Cinzia
collection PubMed
description BACKGROUND: Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biological entities constituted by NBTs with different ploidy status. METHODS: Gene expression profiling of 49 diagnostic primary NBTs with ploidy data was performed using oligonucleotide microarray. Further analyses using Quantitative Real-Time Polymerase Chain Reaction (Q-PCR); array-Comparative Genomic Hybridization (aCGH); and Fluorescent in situ Hybridization (FISH) were performed to investigate the correlation between aneuploidy, chromosomal changes and gene expression profiles. RESULTS: Gene expression profiling of 49 primary near-triploid and near-diploid/tetraploid NBTs revealed distinct expression profiles associated with each NBT subgroup. A statistically significant portion of genes mapped to 1p36 (P = 0.01) and 17p13-q21 (P < 0.0001), described as recurrently altered in NBTs. Over 90% of these genes showed higher expression in near-triploid NBTs and the majority are involved in cell differentiation pathways. Specific chromosomal abnormalities observed in NBTs, 1p loss, 17q and whole chromosome 17 gains, were reflected in the gene expression profiles. Comparison between gene copy number and expression levels suggests that differential expression might be only partly dependent on gene copy number. Intratumoural clonal heterogeneity was observed in all NBTs, with marked interclonal variability in near-diploid/tetraploid tumours. CONCLUSION: NBTs with different cellular DNA content display distinct transcriptional profiles with a significant portion of differentially expressed genes mapping to specific chromosomal regions known to be associated with outcome. Furthermore, our results demonstrate that these specific genetic abnormalities are highly heterogeneous in all NBTs, and suggest that NBTs with different ploidy status may result from different mechanisms of aneuploidy driving tumourigenesis.
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spelling pubmed-25311302008-09-06 Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status Lavarino, Cinzia Garcia, Idoia Mackintosh, Carlos Cheung, Nai-Kong V Domenech, Gema Ríos, José Perez, Noelia Rodríguez, Eva de Torres, Carmen Gerald, William L Tuset, Esperanza Acosta, Sandra Beleta, Helena de Álava, Enrique Mora, Jaume BMC Med Genomics Research Article BACKGROUND: Neuroblastic tumours (NBTs) represent a heterogeneous spectrum of neoplastic diseases associated with multiple genetic alterations. Structural and numerical chromosomal changes are frequent and are predictive parameters of NBTs outcome. We performed a comparative analysis of the biological entities constituted by NBTs with different ploidy status. METHODS: Gene expression profiling of 49 diagnostic primary NBTs with ploidy data was performed using oligonucleotide microarray. Further analyses using Quantitative Real-Time Polymerase Chain Reaction (Q-PCR); array-Comparative Genomic Hybridization (aCGH); and Fluorescent in situ Hybridization (FISH) were performed to investigate the correlation between aneuploidy, chromosomal changes and gene expression profiles. RESULTS: Gene expression profiling of 49 primary near-triploid and near-diploid/tetraploid NBTs revealed distinct expression profiles associated with each NBT subgroup. A statistically significant portion of genes mapped to 1p36 (P = 0.01) and 17p13-q21 (P < 0.0001), described as recurrently altered in NBTs. Over 90% of these genes showed higher expression in near-triploid NBTs and the majority are involved in cell differentiation pathways. Specific chromosomal abnormalities observed in NBTs, 1p loss, 17q and whole chromosome 17 gains, were reflected in the gene expression profiles. Comparison between gene copy number and expression levels suggests that differential expression might be only partly dependent on gene copy number. Intratumoural clonal heterogeneity was observed in all NBTs, with marked interclonal variability in near-diploid/tetraploid tumours. CONCLUSION: NBTs with different cellular DNA content display distinct transcriptional profiles with a significant portion of differentially expressed genes mapping to specific chromosomal regions known to be associated with outcome. Furthermore, our results demonstrate that these specific genetic abnormalities are highly heterogeneous in all NBTs, and suggest that NBTs with different ploidy status may result from different mechanisms of aneuploidy driving tumourigenesis. BioMed Central 2008-08-13 /pmc/articles/PMC2531130/ /pubmed/18700951 http://dx.doi.org/10.1186/1755-8794-1-36 Text en Copyright © 2008 Lavarino et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lavarino, Cinzia
Garcia, Idoia
Mackintosh, Carlos
Cheung, Nai-Kong V
Domenech, Gema
Ríos, José
Perez, Noelia
Rodríguez, Eva
de Torres, Carmen
Gerald, William L
Tuset, Esperanza
Acosta, Sandra
Beleta, Helena
de Álava, Enrique
Mora, Jaume
Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status
title Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status
title_full Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status
title_fullStr Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status
title_full_unstemmed Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status
title_short Differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status
title_sort differential expression of genes mapping to recurrently abnormal chromosomal regions characterize neuroblastic tumours with distinct ploidy status
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2531130/
https://www.ncbi.nlm.nih.gov/pubmed/18700951
http://dx.doi.org/10.1186/1755-8794-1-36
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