The goals of this study are to identify and evaluate molecular markers useful in the classification and grading of gliomas. The intended projects, as listed in the Specific Aims, were selected so as to address problems in tumor classification whose resolution, we believe, will significantly improve the diagnosis, and therefore treatment, of patients with brain tumors. These issues include: (1) the details and diagnostic specificity of molecular changes in spectrum of pilocystic astrocytomas arising in both patients with neurofibromatosis 1 and in the general population without a recognized genetic predisposition to this common pediatric neoplasm, (2) the presence or absence of similar molecular changes in sporadic non-pilocystic tumors (high grade fibrillary astrocytic tumors and oligodendrogliomas) and how these might be related to tumor classification, (3) the prognostic utility in higher grade astrocytic neoplasms of the cycling cell marker Ki-67 and amplification of the epidermal growth factor receptor gene, (4) the genomic abnormalities associated with tumor progression in fibrillary astrocytic and oligodendroglial neoplasms, and how these changes can be used in tumor grading and prognosis, and (5) the determination of tumor extent (staging) of the untreated glioblastoma by unambiguous molecular methods. The proposed research benefits from strong interactions with the multicenter CNS Consortium New Approaches to Brain Tumor Therapy (NABTT). NABTT will provide ready access to rare tissue resources and the extensive clinical and scientific data from a large collection of patients diagnosed with primary gliomas required for our analyses. Our molecular findings derived from PCR-based highly efficient methods will be correlated with clinical parameters including the response to specific NABTT initiated treatments. Close interactions between our Cooperative Glioma Network multidisciplinary research team and the NABTT will significantly extend the resources of both studies. These studies will improve our knowledge of the molecular alterations of these tumors and provide diagnostic markers that can be correlated with outcome. Moreover, these data will provide the basis for future studies on the pathophysiologic mechanisms of gliomas and lead to new approaches to treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA064928-04
Application #
2608118
Study Section
Special Emphasis Panel (SRC (90))
Program Officer
Jacobson, James W
Project Start
1995-01-19
Project End
2000-11-30
Budget Start
1997-12-01
Budget End
2000-11-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Perry, Arie; Aldape, Kenneth D; George, David H et al. (2004) Small cell astrocytoma: an aggressive variant that is clinicopathologically and genetically distinct from anaplastic oligodendroglioma. Cancer 101:2318-26
Popko, Brian; Pearl, Dennis K; Walker, Diane M et al. (2002) Molecular markers that identify human astrocytomas and oligodendrogliomas. J Neuropathol Exp Neurol 61:329-38
Burger, P C; Minn, A Y; Smith, J S et al. (2001) Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma. A study of paraffin-embedded sections. Mod Pathol 14:842-53
Burger, P C; Pearl, D K; Aldape, K et al. (2001) Small cell architecture--a histological equivalent of EGFR amplification in glioblastoma multiforme? J Neuropathol Exp Neurol 60:1099-104
Thomas, C; Ely, G; James, C D et al. (2001) Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells. Acta Neuropathol (Berl) 101:605-15
Smith, J S; Perry, A; Borell, T J et al. (2000) Alterations of chromosome arms 1p and 19q as predictors of survival in oligodendrogliomas, astrocytomas, and mixed oligoastrocytomas. J Clin Oncol 18:636-45
Brat, D J; Hirose, Y; Cohen, K J et al. (2000) Astroblastoma: clinicopathologic features and chromosomal abnormalities defined by comparative genomic hybridization. Brain Pathol 10:342-52
Li, Q; Ahuja, N; Burger, P C et al. (1999) Methylation and silencing of the Thrombospondin-1 promoter in human cancer. Oncogene 18:3284-9
Yates, A J; Franklin, T K; Scheithauer, B W et al. (1999) Sex- and age-related differences in ceramide dihexosides of primary human brain tumors. Lipids 34:1-4
Yates, A J; Comas, T; Scheithauer, B W et al. (1999) Glycolipid markers of astrocytomas and oligodendrogliomas. J Neuropathol Exp Neurol 58:1250-62

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