Sandra Preissig Bigner
Professor Emeritus of Pathology
CYTOGENETICS AND MOLECULAR GENETICS OF BRAIN TUMORS
SANDRA H. BIGNER, M.D.
PROFESSOR OF PATHOLOGY
The long-term goal of this program is to use cytogenetic and molecular genetic approaches to understand mechanisms of growth control of human gliomas. During the past several years cytogenetic analysis and allelotyping of tumors of all grades and histologic types have been used to determine chromosomes and chromosomal regions which are critical to the development and progression of these tumors. We have demonstrated that the most prevalent cytogenetic alterations in glioblastoma are gains of chromosome 7, losses of chromosomes 10 and 9p and the presence of double minute chromosomes (DMs). The majority of tumors with DMs have amplification of the epidermal growth factor receptor gene, loss of 9p is probably associated with deletion of the Multiple Tumor Suppressor 1 (MTS1) gene, and most tumors with 17p loss have mutations of the TP53 gene but the relevant genes on chromosomes 7 remains unknown. The specific region of chromosome 10 which are deleted in the majority of glioblastomas has been localized by deletion mapping to 19q22 the locus for the PTEN gene, 10q25 and 10p. Loss of heterozygosity (LOH) and comparative genomic hybridization (CGH) studies have demonstrated consistent losses of 1p and 19q in oligodendrogliomas. The definition of these specific chromosomal and genetic abnormalities in specific subtypes of gliomas has allowed us to construct a new glioma classification scheme which we are evaluating for its clinical and prognostic significance.
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