Gliomas are a significant cause of morbidity and mortality, and thus have been the focus of frequent basic biologic, basic genetic, and clinical investigations. Numerous genetic and biologic alterations associated with gliomas have been described. However, many of the specific genes involved in gliomas have yet to be identified. A great deal still needs to be learned about the mechanisms by which the known genes are involved in the pathogenesis of gliomas. Furthermore, while much has been learned about the biology and genetics of gliomas, little of this information has been translated into clinical practice. There are still problems with the morphologic classification of gliomas - especially oligodendrogliomas and mixed oligoastrocytomas. It is difficult to predict which patients with anaplastic astrocytomas will suffer early recurrence. And while some gliomas with specific genetic alterations seem to respond to chemotherapy (e.g., Cairncross et al., JNCI 90:1473,1998), these observations need to be confirmed and extended and additional therapeutic genetic targets identified and/or developed. Through four projects and two cores this program, which builds on the past experience of the Glioma Marker Network (GMN) consortium, will study the basic biology of several specific biochemical and genetic alterations associated with gliomas. It will also continue to evaluate the predictive, prognostic, and pathologic relevance of these alterations. Project 1 will study the biologic and clinical relevance of 7q gain in gliomas, with emphasis on the mechanism by which this alteration predicts a poorer prognosis. Project 2 will evaluate the function of mutated and amplified EGFR in gliomas and will test several potential therapeutic approaches targeting these mutant receptors. Project 3 will identify and study the function of the 19q gene associated with gliomas and associated with a prolonged response of some gliomas to chemotherapy. Project 4 will study the biologic and clinical relevance of glycolipid and glycosyltransferase alterations in gliomas. Thus, through these projects, this highly-interactive and experienced program will make significant progress toward understanding the pathogenesis of gliomas, and translating this knowledge into new diagnostic and therapeutic tools.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA085799-02S1
Application #
6642508
Study Section
Subcommittee G - Education (NCI)
Program Officer
Rosenfeld, Bobby
Project Start
2001-06-14
Project End
2005-05-31
Budget Start
2002-06-01
Budget End
2003-05-31
Support Year
2
Fiscal Year
2002
Total Cost
$123,187
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

Showing the most recent 10 out of 21 publications