TCGA's Study of Glioblastoma Multiforme
What is glioblastoma multiforme?
Glioblastoma Multiforme (GBM) is a fast-growing type of malignant brain tumor that is the most common brain tumor in adults. In 2010, more than 22,000 Americans were estimated to have been diagnosed and 13,140 were estimated to have died from brain and other nervous system cancers.1 GBM accounts for about 15% of all brain tumors and occurs in adults between the ages of 45 and 70 years.2 Patients with GBM have a poor prognosis and usually survive less than 15 months following diagnosis. Currently there are no effective long-term treatments for this disease. Additional information on brain tumors.
What have TCGA researchers learned about GBM?
- A novel subtype of GBM, established by TCGA, affects younger adults and has an increased survival rate. These tumors are distinguished by a methylation signature which may account for the improved survival of these patients.
- Four distinct molecular subtypes of GBM respond differently to aggressive therapies: proneural, neural, classical, and mesenchymal.
- Selective pressue to lose mismatch repair function may cause some tumors to become resistant to therapy after treatment with a standard chemotherapy called temozolomide. This finding could be used to develop new strategies that will not activate this drug resistance mechanism.
- Alterations of the EGFR gene as well as a region on a chromosome containing MDM2 and CDK4 genes may be important to the development of GBM.
- Pinpointed five gene mutations that may provide new insights into the biology of this disease:
- NF1, a gene identified as the cause of a rare inherited disorder called neurofibromatosis
- ERBB2, a gene involved in breast cancer
- TP53, a gene involved in many types of cancers
- PIK3R1, a gene that controls an enzyme that is found in many cancers
- TERT, a gene that encodes for an enzyme that maintains the protective structures, known as telomeres, covering the ends of chromosomes
- GBM mutations are enriched for chromatin modification genes.
1American Cancer Society. Cancer Facts and Figures 2010. Atlanta: American Cancer Society, Inc. 2010.
2Levin VA, Leibel SA, Gutin PH: Neoplasms of the central nervous system. In: DeVita VT Jr, Hellman S, Rosenberg SA ed. Cancer: Principles and Practice of Oncology. 6th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001: 2100-60.