Cargando…

Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma

BACKGROUND: Glioblastoma arises from complex interactions between a variety of genetic alterations and environmental perturbations. Little attention has been paid to understanding how genetic variations, altered gene expression and microRNA (miRNA) expression are integrated into networks which act t...

Descripción completa

Detalles Bibliográficos
Autores principales: Dong, Hua, Luo, Li, Hong, Shengjun, Siu, Hoicheong, Xiao, Yanghua, Jin, Li, Chen, Rui, Xiong, Momiao
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002314/
https://www.ncbi.nlm.nih.gov/pubmed/21114830
http://dx.doi.org/10.1186/1752-0509-4-163
_version_ 1782193728987856896
author Dong, Hua
Luo, Li
Hong, Shengjun
Siu, Hoicheong
Xiao, Yanghua
Jin, Li
Chen, Rui
Xiong, Momiao
author_facet Dong, Hua
Luo, Li
Hong, Shengjun
Siu, Hoicheong
Xiao, Yanghua
Jin, Li
Chen, Rui
Xiong, Momiao
author_sort Dong, Hua
collection PubMed
description BACKGROUND: Glioblastoma arises from complex interactions between a variety of genetic alterations and environmental perturbations. Little attention has been paid to understanding how genetic variations, altered gene expression and microRNA (miRNA) expression are integrated into networks which act together to alter regulation and finally lead to the emergence of complex phenotypes and glioblastoma. RESULTS: We identified association of somatic mutations in 14 genes with glioblastoma, of which 8 genes are newly identified, and association of loss of heterozygosity (LOH) is identified in 11 genes with glioblastoma, of which 9 genes are newly discovered. By gene coexpression network analysis, we indentified 15 genes essential to the function of the network, most of which are cancer related genes. We also constructed miRNA coexpression networks and found 19 important miRNAs of which 3 were significantly related to glioblastoma patients' survival. We identified 3,953 predicted miRNA-mRNA pairs, of which 14 were previously verified by experiments in other groups. Using pathway enrichment analysis we also found that the genes in the target network of the top 19 important miRNAs were mainly involved in cancer related signaling pathways, synaptic transmission and nervous systems processes. Finally, we developed new methods to decipher the pathway connecting mutations, expression information and glioblastoma. We indentified 4 cis-expression quantitative trait locus (eQTL): TP53, EGFR, NF1 and PIK3C2G; 262 trans eQTL and 26 trans miRNA eQTL for somatic mutation; 2 cis-eQTL: NRAP and EGFR; 409 trans- eQTL and 27 trans- miRNA eQTL for lost of heterozygosity (LOH) mutation. CONCLUSIONS: Our results demonstrate that integrated analysis of multi-dimensional data has the potential to unravel the mechanism of tumor initiation and progression.
format Text
id pubmed-3002314
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-30023142011-01-06 Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma Dong, Hua Luo, Li Hong, Shengjun Siu, Hoicheong Xiao, Yanghua Jin, Li Chen, Rui Xiong, Momiao BMC Syst Biol Research Article BACKGROUND: Glioblastoma arises from complex interactions between a variety of genetic alterations and environmental perturbations. Little attention has been paid to understanding how genetic variations, altered gene expression and microRNA (miRNA) expression are integrated into networks which act together to alter regulation and finally lead to the emergence of complex phenotypes and glioblastoma. RESULTS: We identified association of somatic mutations in 14 genes with glioblastoma, of which 8 genes are newly identified, and association of loss of heterozygosity (LOH) is identified in 11 genes with glioblastoma, of which 9 genes are newly discovered. By gene coexpression network analysis, we indentified 15 genes essential to the function of the network, most of which are cancer related genes. We also constructed miRNA coexpression networks and found 19 important miRNAs of which 3 were significantly related to glioblastoma patients' survival. We identified 3,953 predicted miRNA-mRNA pairs, of which 14 were previously verified by experiments in other groups. Using pathway enrichment analysis we also found that the genes in the target network of the top 19 important miRNAs were mainly involved in cancer related signaling pathways, synaptic transmission and nervous systems processes. Finally, we developed new methods to decipher the pathway connecting mutations, expression information and glioblastoma. We indentified 4 cis-expression quantitative trait locus (eQTL): TP53, EGFR, NF1 and PIK3C2G; 262 trans eQTL and 26 trans miRNA eQTL for somatic mutation; 2 cis-eQTL: NRAP and EGFR; 409 trans- eQTL and 27 trans- miRNA eQTL for lost of heterozygosity (LOH) mutation. CONCLUSIONS: Our results demonstrate that integrated analysis of multi-dimensional data has the potential to unravel the mechanism of tumor initiation and progression. BioMed Central 2010-11-29 /pmc/articles/PMC3002314/ /pubmed/21114830 http://dx.doi.org/10.1186/1752-0509-4-163 Text en Copyright ©2010 Dong 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
Dong, Hua
Luo, Li
Hong, Shengjun
Siu, Hoicheong
Xiao, Yanghua
Jin, Li
Chen, Rui
Xiong, Momiao
Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma
title Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma
title_full Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma
title_fullStr Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma
title_full_unstemmed Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma
title_short Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma
title_sort integrated analysis of mutations, mirna and mrna expression in glioblastoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002314/
https://www.ncbi.nlm.nih.gov/pubmed/21114830
http://dx.doi.org/10.1186/1752-0509-4-163
work_keys_str_mv AT donghua integratedanalysisofmutationsmirnaandmrnaexpressioninglioblastoma
AT luoli integratedanalysisofmutationsmirnaandmrnaexpressioninglioblastoma
AT hongshengjun integratedanalysisofmutationsmirnaandmrnaexpressioninglioblastoma
AT siuhoicheong integratedanalysisofmutationsmirnaandmrnaexpressioninglioblastoma
AT xiaoyanghua integratedanalysisofmutationsmirnaandmrnaexpressioninglioblastoma
AT jinli integratedanalysisofmutationsmirnaandmrnaexpressioninglioblastoma
AT chenrui integratedanalysisofmutationsmirnaandmrnaexpressioninglioblastoma
AT xiongmomiao integratedanalysisofmutationsmirnaandmrnaexpressioninglioblastoma