Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Export

@article{citeulike:3203932, abstract = {Human cancer cells typically harbour 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 multi-dimensional 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--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. 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.}, address = {A list of participants and affiliations appears at the end of the paper.}, author = {{Cancer Genome Atlas Research Network}}, booktitle = {Nature}, citeulike-article-id = {3203932}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature07385}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature07385}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18772890}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18772890}, day = {23}, doi = {10.1038/nature07385}, issn = {1476-4687}, journal = {Nature}, keywords = {acgh, cancer, expression, gbm, integration, sequencing, tcga}, month = {October}, number = {7216}, pages = {1061--1068}, posted-at = {2009-06-05 01:18:37}, priority = {0}, publisher = {Nature Publishing Group}, title = {Comprehensive genomic characterization defines human glioblastoma genes and core pathways.}, url = {http://dx.doi.org/10.1038/nature07385}, volume = {455}, year = {2008} }

TY - JOUR ID - citeulike:3203932 L3 - citeulike-article-id:3203932 N2 - Human cancer cells typically harbour 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 multi-dimensional 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--the most common type of adult brain cancer--and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. 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. IS - 7216 JF - Nature SN - 1476-4687 AD - A list of participants and affiliations appears at the end of the paper. EP - 1068 TI - Comprehensive genomic characterization defines human glioblastoma genes and core pathways. PB - Nature Publishing Group VL - 455 T2 - Nature SP - 1061 KW - acgh KW - cancer KW - expression KW - gbm KW - integration KW - sequencing KW - tcga PY - 2008/10/23/ UR - http://dx.doi.org/10.1038/nature07385 ER -