- Purpose:
To determine the predictive value of the genetic profile of a primary glioma by correlation of this profile with type, grade and genetic profile of the recurrence.
- Plan of investigation:
The gliomas (astrocytomas, oligodendrogliomas, and ependymomas) constitute a heterogeneous group of brain tumors. They are the most frequent neoplasms in the central nervous system. Important prognostic parameters in case of glioma are age and performance status of the patient and tumor type and grade. In general, survival is inversely related to tumor grade. However, there is considerable variation in survival time between individual patients within one malignancy grade. Gliomas usually recur, often with a higher grade and sometimes with a different morphology. However, time to recurrence for the individual patients is highly variable and currently cannot be predicted. Accurate diagnosis of the glioma is important since oligodendrogliomas and ependymomas have a far better prognosis than high grade astrocytomas and oligodendrogliomas are susceptible to chemotherapy. However, accurate histologic typing of gliomas can be problematic because of the frequent heterogeneity in type and grade within one tumor and because of the increasing neurosurgical practice to offer small stereotactic biopsies for histological analysis. We want to determine the additional predictive value of genetic changes in the primary tumor with respect to diagnosis, recurrence and survival. This will be done by establishing genetic profiles of primary tumors and their recurrences and by correlating these profiles with changes in tumor type and grade and with survival of the patient. Genetic profiling will include the analysis of changes at the DNA level and at the level of expression of known and candidate genes implicated in glioma tumorigenesis. As part of this project, we will clone and characterize the glioma progression-associated tumor suppressor gene that we recently assigned to 22q13.3.
- Possible results:
1. Improved diagnosis of glioma, based on its genetic profile
2. Improved prediction of the outcome of disease, based on the genetic profile of the tumor, with respect to tumor recurrence (type, grade, rate) and survival of the individual patient.
3. Identification of genes that are under- or overexpressed in glioma
4. Identification of a new tumor suppressor gene in 22q13.3, implicated in glioma tumorigenesis.
- Relevance for cancer research:
Genetic profiling of a glioma may help in diagnosis of the tumor and in treatment decision. In the proposed investigation we will identify genes, including a putative tumor suppressor gene in 22q13.3, whose dysregulated status is possibly of prognostic significance. Identification of these genes will not only be important for understanding glioma tumorigenesis but possibly also for understanding the genesis of other types of cancer. Finally, knowledge of the genetic factors that cause glioma is a prerequisite for the development of gene-therapeutic and drug-based strategies to cure this hitherto fatal tumor. |
