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Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Human cancer cells typically harbor multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multidimensional analysis of these molecular character...

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Formato: Texto
Lenguaje:English
Publicado: 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671642/
https://www.ncbi.nlm.nih.gov/pubmed/18772890
http://dx.doi.org/10.1038/nature07385
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description Human cancer cells typically harbor multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multidimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here, we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas (GBM), the most common type of adult brain cancer, and nucleotide sequence aberrations in 91 of the 206 GBMs. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the PI3 kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of GBM. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
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spelling pubmed-26716422009-04-23 Comprehensive genomic characterization defines human glioblastoma genes and core pathways Nature Article Human cancer cells typically harbor multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas (TCGA) pilot project aims to assess the value of large-scale multidimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here, we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas (GBM), the most common type of adult brain cancer, and nucleotide sequence aberrations in 91 of the 206 GBMs. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the PI3 kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of GBM. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer. 2008-09-04 2008-10-23 /pmc/articles/PMC2671642/ /pubmed/18772890 http://dx.doi.org/10.1038/nature07385 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Comprehensive genomic characterization defines human glioblastoma genes and core pathways
title Comprehensive genomic characterization defines human glioblastoma genes and core pathways
title_full Comprehensive genomic characterization defines human glioblastoma genes and core pathways
title_fullStr Comprehensive genomic characterization defines human glioblastoma genes and core pathways
title_full_unstemmed Comprehensive genomic characterization defines human glioblastoma genes and core pathways
title_short Comprehensive genomic characterization defines human glioblastoma genes and core pathways
title_sort comprehensive genomic characterization defines human glioblastoma genes and core pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671642/
https://www.ncbi.nlm.nih.gov/pubmed/18772890
http://dx.doi.org/10.1038/nature07385
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