Functional Network Analysis Reveals Extended Gliomagenesis Pathway Maps and Three Novel MYC-Interacting Genes in Human Gliomas Export

@article{citeulike:3078326, abstract = {Gene expression profiling has proven useful in subclassification and outcome prognostication for human glial brain tumors. The analysis of biological significance of the hundreds or thousands of alterations in gene expression found in genomic profiling remains a major challenge. Moreover, it is increasingly evident that genes do not act as individual units but collaborate in overlapping networks, the deregulation of which is a hallmark of cancer. Thus, we have here applied refined network knowledge to the analysis of key functions and pathways associated with gliomagenesis in a set of 50 human gliomas of various histogenesis, using cDNA microarrays, inferential and descriptive statistics, and dynamic mapping of gene expression data into a functional annotation database. Highest-significance networks were assembled around the myc oncogene in gliomagenesis and around the integrin signaling pathway in the glioblastoma subtype, which is paradigmatic for its strong migratory and invasive behavior. Three novel MYC-interacting genes (UBE2C, EMP1, and FBXW7) with cancer-related functions were identified as network constituents differentially expressed in gliomas, as was CD151 as a new component of a network that mediates glioblastoma cell invasion. Complementary, unsupervised relevance network analysis showed a conserved self-organization of modules of interconnected genes with functions in cell cycle regulation in human gliomas. This approach has extended existing knowledge about the organizational pattern of gene expression in human gliomas and identified potential novel targets for future therapeutic development. 10.1158/0008-5472.CAN-05-1204}, author = {Bredel, Markus and Bredel, Claudia and Juric, Dejan and Harsh, Griffith R. and Vogel, Hannes and Recht, Lawrence D. and Sikic, Branimir I.}, citeulike-article-id = {3078326}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/0008-5472.CAN-05-1204}, citeulike-linkout-1 = {http://cancerres.aacrjournals.org/cgi/content/abstract/65/19/8679}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/16204036}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=16204036}, citeulike-linkout-4 = {http://cancerres.aacrjournals.org/cgi/content/full/65/19/8679}, day = {1}, doi = {10.1158/0008-5472.CAN-05-1204}, journal = {Cancer Res}, keywords = {20q, myc, ube2c}, month = {October}, number = {19}, pages = {8679--8689}, posted-at = {2008-08-03 09:02:39}, priority = {2}, title = {Functional Network Analysis Reveals Extended Gliomagenesis Pathway Maps and Three Novel MYC-Interacting Genes in Human Gliomas}, url = {http://dx.doi.org/10.1158/0008-5472.CAN-05-1204}, volume = {65}, year = {2005} }

TY - JOUR ID - citeulike:3078326 L3 - citeulike-article-id:3078326 N2 - Gene expression profiling has proven useful in subclassification and outcome prognostication for human glial brain tumors. The analysis of biological significance of the hundreds or thousands of alterations in gene expression found in genomic profiling remains a major challenge. Moreover, it is increasingly evident that genes do not act as individual units but collaborate in overlapping networks, the deregulation of which is a hallmark of cancer. Thus, we have here applied refined network knowledge to the analysis of key functions and pathways associated with gliomagenesis in a set of 50 human gliomas of various histogenesis, using cDNA microarrays, inferential and descriptive statistics, and dynamic mapping of gene expression data into a functional annotation database. Highest-significance networks were assembled around the myc oncogene in gliomagenesis and around the integrin signaling pathway in the glioblastoma subtype, which is paradigmatic for its strong migratory and invasive behavior. Three novel MYC-interacting genes (UBE2C, EMP1, and FBXW7) with cancer-related functions were identified as network constituents differentially expressed in gliomas, as was CD151 as a new component of a network that mediates glioblastoma cell invasion. Complementary, unsupervised relevance network analysis showed a conserved self-organization of modules of interconnected genes with functions in cell cycle regulation in human gliomas. This approach has extended existing knowledge about the organizational pattern of gene expression in human gliomas and identified potential novel targets for future therapeutic development. 10.1158/0008-5472.CAN-05-1204 IS - 19 JF - Cancer Res EP - 8689 TI - Functional Network Analysis Reveals Extended Gliomagenesis Pathway Maps and Three Novel MYC-Interacting Genes in Human Gliomas VL - 65 SP - 8679 KW - 20q KW - myc KW - ube2c AU - Bredel, Markus AU - Bredel, Claudia AU - Juric, Dejan AU - Harsh, Griffith AU - Vogel, Hannes AU - Recht, Lawrence AU - Sikic, Branimir PY - 2005/10/01/ UR - http://dx.doi.org/10.1158/0008-5472.CAN-05-1204 ER -