Alterations of chromosomes 1 and 19 are frequent events in human gliomas and have recently been suggested to be associated with chemotherapeutic response and prolonged survival in anaplastic oligodendrogliomas. However, the genes on these chromosome arms that are altered in gliomas and potentially associated with chemotherapeutic response and survival have not been identified. Furthermore, the exciting response and survival data have not been confirmed in an appropriately-treated, prospectively-collected cohort of patients nor have these clinical correlations been translated to lower grade oligodendrogliomas or other glial tumors. We have made considerable progress in mapping the genomic location of the 19q gene and have identified several genes in this region. In addition, we have assembled several prospectively-collected cohorts of patients to confirm and extend the clinical observations of Cairncross et al. and Smith et al. In this application, we propose to 1) Complete the identification of the 19q gene (or genes) involved in the development of gliomas, 2) Begin an evaluation of the function of the 19q gene (or genes), and 3) To perform clinical-translational studies designed to validate the postulated predictive value of 1p/19q alterations, to determine if alterations of the specific genes involved have similar associations, and to extend the associations to lower grade tumors and to tumors of different glial lineage. Thus, this project will identify and begin to study the function of the 19q gene and further define the clinical significance of the 1p and 19q alterations. The overall result of this project will be an initial understanding of the genetics and biology of the 19q and 1p genes as well as the development of a combined histologic and genotypic assessment of gliomas that could potentially be used to stratify patients for therapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA085799-02
Application #
6606498
Study Section
Subcommittee E - Prevention &Control (NCI)
Project Start
2002-06-28
Project End
2003-05-31
Budget Start
Budget End
Support Year
2
Fiscal Year
2002
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Phillips, Joanna J; Misra, Anjan; Feuerstein, Burt G et al. (2010) Pituicytoma: characterization of a unique neoplasm by histology, immunohistochemistry, ultrastructure, and array-based comparative genomic hybridization. Arch Pathol Lab Med 134:1063-9
Jenkins, Robert B; Blair, Hilary; Ballman, Karla V et al. (2006) A t(1;19)(q10;p10) mediates the combined deletions of 1p and 19q and predicts a better prognosis of patients with oligodendroglioma. Cancer Res 66:9852-61
Omran, O M; Saqr, H E; Yates, Allan J (2006) Molecular mechanisms of GD3-induced apoptosis in U-1242 MG glioma cells. Neurochem Res 31:1171-80
Saqr, H E; Omran, O; Dasgupta, S et al. (2006) Endogenous GD3 ganglioside induces apoptosis in U-1242 MG glioma cells. J Neurochem 96:1301-14
Saqr, H E; Omran, O M; Oblinger, J L et al. (2006) TRAIL-induced apoptosis in U-1242 MG glioma cells. J Neuropathol Exp Neurol 65:152-61
Oblinger, J L; Pearl, D K; Boardman, C L et al. (2006) Diagnostic and prognostic value of glycosyltransferase mRNA in glioblastoma multiforme patients. Neuropathol Appl Neurobiol 32:410-8
Misra, Anjan; Pellarin, Malgorzata; Hu, Lily et al. (2006) Chromosome transfer experiments link regions on chromosome 7 to radiation resistance in human glioblastoma multiforme. Genes Chromosomes Cancer 45:20-30
Nigro, Janice M; Misra, Anjan; Zhang, Li et al. (2005) Integrated array-comparative genomic hybridization and expression array profiles identify clinically relevant molecular subtypes of glioblastoma. Cancer Res 65:1678-86
Misra, Anjan; Pellarin, Malgorzata; Nigro, Janice et al. (2005) Array comparative genomic hybridization identifies genetic subgroups in grade 4 human astrocytoma. Clin Cancer Res 11:2907-18
Law, Mark E; Templeton, Kristen L; Kitange, Gaspar et al. (2005) Molecular cytogenetic analysis of chromosomes 1 and 19 in glioma cell lines. Cancer Genet Cytogenet 160:1-14

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