EARLY GENETIC EVENTS IN ASTROCYTOMA FORMATION

Project: Research project

Project Details

Description

DESCRIPTION (adapted from applicant's abstract): Astrocytomas of the adult
cerebral hemispheres are among the most deadly of all human tumors. Although
much is known about the genetic alterations in malignant gliomas, there is much
less information about the initial genetic events leading to the formation of
low-grade astrocytomas (LGA). Many LGAs undergo anaplastic progression over
months to years, evolving towards GBM. This evolution results in initial phase
in tumor formation that is characterized by a small burden of genetic changes
on downstream events and tumor behavior has been difficult to study because of
the relative rarity of LGA patients, compared to patients with malignant
astrocytomas.

Analysis of the genetic changes in high-grade astrocytomas have suggested the
presence of distinct disease entities that are manifested in different age
groups and develop through different genetic pathways. Alterations of p53 and
EGFR, for instance are mutually exclusive events in secondary and de novo GBM.
Some genetic changes, such as p53, occur at the same frequency across all
grades of astrocytoma, suggesting that these genes have a role in initial tumor
formation.

The investigators hypothesize that the molecular patterns defining specific
subsets of gliomas are determined at the time of LGA formation, and that the
initial genotype correlates with the rate of anaplastic progression and
survival, and will as with subsequent genetic changes. They propose to test
this hypothesis in a cohort of LGA patients with the goals of: 1) understanding
early events in glioma formation, 2) understanding the molecular basis of
anaplastic progression, and 3) gaining the ability to better predict clinical
tumor behavior.

For this purpose, they propose to obtain a large, multi-institutional,
retrospective sample of LGAs, with well-defined clinical follow up, and
adequate tissue for histologic and molecular studies. They will characterize
specific genetics alterations, and test for correlations between subsets of
these alteration and clinical and biological behavior of the tumors. They will
examine genetic changes in tumors at the time of anaplastic progression for
those cases in which tumor material is available. As a way forward to new
hypotheses, they will determine genome-wide changes in subsets of LGA patients
with good and poor outcomes using comparative genomic hybridization (CGH).
StatusNot started

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