Information for the General Public

Adult Brain Tumors

Glioblastoma multiforme is the most common primary malignant brain tumor in adults.  Approximately 10,000 people per year in the United States are diagnosed with a glioblastoma multiforme and a similar number of people die each year from this disease.  Presenting symptoms range from the subtle to the dramatic including headaches, focal neurologic deficits, altered mental status, personality changes, and seizures.  Treatment of these devastating tumors requires a multidisciplinary approach with contributions from neurosurgery, radiation oncology, and neuro-oncology and neurology.  Despite advances in all avenues of treatment, prognosis remains poor.  Five-year survival remains less than 5%.  We continue to try to understand the biology of this disease and discoveries have led to several new approaches to treatment including immunotherapy and gene therapy.  These novel approaches as well as ones sure to come hold promise for combating this devastating disease. Within the Departments of Neurosurgery and Cell and Developmental Biology at the University of Michigan, our team is developing novel experimental therapies with the aim of providing safe and efficacious approaches for the treatment of brain tumors. We anticipate that a significant improvement in patient survival will stem from the combination of several agents, including gene therapy, vaccination and small molecules.


Pediatric Brain Tumors

Brain tumors are the leading cause of cancer-related mortality in children. Pediatric glioblastoma remains one of the most difficult childhood tumors to treat, as 70-90% of patients will die within the first two years of receiving this diagnosis. Despite histologic similarities, pediatric GBM is a distinct tumor from adult GBM at the molecular level. In genome-wide sequencing of pediatric GBM tumors, distinct alterations are seen in pediatric GBM. Mutations are seen in the histone gene H3F3A in 36%% of pediatric tumors, but only 3% of adult GBMs (all in young adults). There is an overlap of these mutations with p53 mutations, and p53 mutations are more frequently seen than in adult tumors. Further, copy number alterations in genes within
 the “core pathways” of adult GBM are seen at much lower frequency in pediatric GBMs. Gene expression profiles of pediatric GBM tumors are also distinct from adult GBM tumors, with significantly increased expression of gene sets associated with PDGFRA amplification, and down-regulation of the gene sets associated with EGFR-amplification. Other clinical aspects of pediatric GBM point to biological distinctions including lower rates of malignant transformation of lower grade astrocytomas. As well, a significant proportion of pediatric high-grade gliomas are located in the thalamus and brainstem, which is only rarely seen in adults. Initial treatment for pediatric GBM is similar to adult GBM with attempt for radical resection followed by radiation, usually with concurrent temozolomide. However, the addition of temozolomide to irradiation in pediatric patients does not appear to offer a survival advantage as it does in adult GBM.


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