Over the last few years, a number of studies using genomic data from glioma patients have allowed researchers to identify several DNA sequencing variations in genes that are associated with the development of oligodendroglioma and astrocytoma tumors. The important word here is "associated." The studies did not identify the actual causative genetic alterations, but demonstrate a relationship between these specific variations and risk of developing a glioma.

Drs. Robert Jenkins and Margaret Wrensch of the Mayo Clinic Cancer Center and University of California San Francisco, respectively, along with others, had previously identified that variations on chromosome 8 near a specific gene called CCDC26 are risk indicators for developing oligodendrogliomas and astrocytomas with mutated IDH1 or IDH2 genes.

Recently, Drs. Jenkins and Wrensch performed a careful mapping study of chromosome 8 to identify higher risk and/or low-frequency genetic variations near the CCDC26 gene, as well as another gene called cMYC. The study found seven low-frequency variations were identified as being associated with glioma risk. Of greatest interest was that of the rare and highly potent genetic alteration rs55705857. This variant was associated with a 6-fold elevated risk of developing oligodendroglioma and astrocytoma tumors that harbor IDH mutations. Such a risk is similar to that of the risk of developing breast cancer in women who are BRCA1 or BRCA2 mutation carriers.

These findings suggest that many oligodendrogliomas and astrocytomas may be congenital tumors. Gaining a better understanding of how these gliomas develop in a predisposed background will have a major implication for family members in terms of prevention and early detection.

In addition, this work may lead to many important therapeutic benefits for those individuals burdened with a brain tumor. Knowing the genomic variation(s) that leads to development of these gliomas enables researchers to build models that represent the disease from its initiation. This will allow researchers to not only test therapeutic approaches in earlier stage oligodendroglioma, but will also allow for the discovery of new drugs that could potentially eradicate tumor cells early in the disease.

Additionally, it is known that oligodendroglioma grade II/III tumors are generally sensitive to radiation and chemotherapy. By modeling the early stages of these tumors, there is the opportunity to better understand the mechanisms that drive oligodendrogliomas (grade II) to high-grade gliomas (grade III/IV), and perhaps use this information to alter other similar tumors, making them sensitive to treatment as well.

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