Molecular Markers of Glioma Initiation and Progression

DESCRIPTION: (provided by Applicant)
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.