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  • 1
    Keywords: CANCER ; EXPRESSION ; GROWTH-FACTOR ; SURVIVAL ; tumor ; LONG-TERM ; GENE ; DELETION ; PROGRESSION ; AMPLIFICATION ; MUTATIONS ; expression profiling ; MALIGNANT BRAIN-TUMORS ; ONCOLOGY ; genetic pathways ; astrocytoma ; GLIOBLASTOMA-MULTIFORME ; GLIOBLASTOMA ; ARRAY-CGH ; FGFR2 ; INTEGRATED GENOMIC ANALYSIS ; IDH
    Abstract: To identify novel glioma-associated pathomechanisms and molecular markers, we performed an array-based comparative genomic hybridization analysis of 131 diffuse astrocytic gliomas, including 87 primary glioblastomas (pGBIV), 13 secondary glioblastomas (sGBIV), 19 anaplastic astrocytomas (AAIII) and 12 diffuse astrocytomas (AII). All tumors were additionally screened for IDH1 and IDH2 mutations. Expression profiling was performed for 74 tumors (42 pGBIV, 11 sGBIV, 13 AAIII, 8 AII). Unsupervised and supervised bioinformatic analyses revealed distinct genomic and expression profiles separating pGBIV from the other entities. Classifier expression signatures were strongly associated with the IDH1 gene mutation status. Within pGBIV, the rare subtype of IDH1 mutant tumors shared expression profiles with IDH1 mutant sGBIV and was associated with longer overall survival compared with IDH1 wild-type tumors. In patients with IDH1 wild-type pGBIV, PDGFRA gain or amplification as well as 19q gain were associated with patient outcome. Array-CGH analysis additionally revealed homozygous deletions of the FGFR2 gene at 10q26.13 in 2 pGBIV, with reduced FGFR2 mRNA levels being frequent in pGBIV and linked to poor outcome. In conclusion, we report that diffuse astrocytic gliomas can be separated into 2 major molecular groups with distinct genomic and mRNA profiles as well as IDH1 gene mutation status. In addition, our results suggest FGFR2 as a novel glioma-associated candidate tumor suppressor gene on the long arm of chromosome 10.
    Type of Publication: Journal article published
    PubMed ID: 20473936
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  • 2
    Keywords: RECEPTOR ; APOPTOSIS ; CANCER ; SURVIVAL ; tumor ; Germany ; THERAPY ; DIAGNOSIS ; DISEASE ; PATIENT ; treatment ; PARTICLES ; STAGE ; REGIONS ; CHRONIC LYMPHOCYTIC-LEUKEMIA ; TRANSLATION ; LEVEL ; cancer research ; CANCERS
    Abstract: Background: Despite great advances in basic oncology research, the situation in clinical oncology continues to be dissatisfying. Reasons for this include a lack of highly effective and specific types of treatment, late diagnosis of cancers (i.e., in advanced stages) and poor translation of new research results into clinical practice. Basic Situation: Knowledge in cancer research his grown exponentially over the past 2 decides. While our understanding of cancer development at the molecular level continues to improve, the actual transfer of these findings into practice is lagging behind today's possibilities. Examples from the German Cancer Research Center ("Deutsches Krebsforschungszentrum" [DKFZ]) and numerous other research institutes show that novel approaches in diagnostics and therapy do exist. Solution: To close the gap between basic research and clinical practice, completely new organizational forms in oncology are needed. Intelligent 0 models of integrated care of tumor patients shaped after US Comprehensive Cancer Centers may lead to fundamental improvements in clinical oncology, opening LIP a way to closely interlock research and clinical practice in order to create synergies for both sides. Such models are currently being established in different places in Germany, with the National Center for Tumor Diseases (NCT) Heidelberg occupying a special place due to its affiliation with the German Cancer Research Center. Moreover, collaboration with industry engaged in research needs to be intensified in order to advance new approaches in research to market readiness. Outlook: Cancer medicine of the future will be more specific, more individual and more interdisciplinary thin it is today. Cancer research, clinical oncology and industry engaged in research need to join forces in a strong alliance for the transfer of scientific findings into clinical application
    Type of Publication: Journal article published
    PubMed ID: 16501913
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