Mutations in IDH1 or IDH2 are found in roughly 70 percent of low- and intermediate-grade gliomas, but usually not in primary forms of a more aggressive form of brain cancer, glioblastoma. Secondary glioblastomas that come from lower-grade gliomas do have the mutations.
SEER: The five–year relative survival rate following diagnosis of a primary malignant brain and central nervous system tumor (including lymphomas and leukemias, tumors of the pituitary and pineal glands, and olfactory tumors of the nasal cavity) is 32.3% for males and 35.5% for females (1995–2008 data).
SEER: Five–year relative survival rates following diagnosis of a primary malignant brain and central nervous system tumor (including lymphomas and leukemias, tumors of the pituitary and pineal glands, and olfactory tumors of the nasal cavity) by age of diagnosis (1995–2008 data):
Age 0-19 years: 72.6% Age 55-64 years: 17.7%
Age 20-44 years: 57.1% Age 65-74 years: 10.0%
Age 45-54 years: 31.6% Age 75 or older: 5.6%
To verify the test as a diagnostic tool, DNA from 65 glioma patients’ biopsy samples was analyzed; 39 had mutations in IDH1 or IDH2. Magnetic resonance spectroscopic analysis of the samples could predict the presence of the mutation with 98 percent accuracy.
The technique uses magnetic resonance imaging equipment that is already widely used in hospitals for diagnostic imaging , but modifies the detection method in order to detect 2-hydroxyglutarate. No injections or special equipment would be needed for clinical use, Mao says.
“We wanted to establish the feasibility of detecting 2HG using FDA-approved scanners that are currently available in the clinic, over a time period that is tolerable to the patient – in about 20 or 30 minutes,” he says.
Brain Cancer Incidence and Prevalence
In the United States, the annual incidence of brain cancer generally is 15–20 cases per 100,000 people. Brain cancer is the leading cause of cancer-related death in patients younger than age 35.
Primary brain tumors account for 50% of intracranial tumors and secondary brain cancer accounts for the remaining cases. Approximately 19,000 people in the United States are diagnosed with primary cancer each year and about 13,000 die of the disease. The annual incidence of primary brain cancer in children is about 3 per 100,000.
Secondary brain cancer occurs in 20–30% of patients with metastatic disease and incidence increases with age. In the United States, about 100,000 cases of secondary brain cancer are diagnosed each year.
MRS has been used to monitor therapeutic progress for brain cancer patients. In contrast with the new technique, established methods measure chemicals that are present in healthy tissues and cannot distinguish 2HG from the other chemicals in the brain.
Recent research indicates that 2-hydroxyglutarate accumulation leads to the activation of genes that are usually shut off in healthy cells. Several laboratories are looking for ways to reverse the metabolic changes in the IDH1/2-mutated cells as a form of targeted therapy.
The research was supported by the National Cancer Institute, the Atlanta Clinical and Translational Science Institute, the Georgia Cancer Coalition, and the Brain Tumor Funders Collaborative.
J. Kalinina, A. Carroll, L. Wang, Q. Yu, D.E. Mancheno, S. Wu, F. Liu, J. Ahn, M. He, H. Mao and E.G. Van Meir. Detection of “oncometabolite” 2-hydroxyglutarate by magnetic resonance analysis as a biomarker of IDH1/2 mutations in glioma. J. Mol. Med. online first (2012).