Molecular pathology of gliomas

Gliomas are the most common primary neoplasms of the brain. They are a heterogeneous group of tumours characterized by infiltrative growth, and relative resistance to radiotherapy and chemotherapy. Glioblastomas have complex chromosomal aberrations including amplifications and gains of 7p, 12q13–q21, and chromosome 19, and losses are 10q, 9p, 13q and 22q, whereas the karyotypes of pilocytic astrocytomas show only limited changes. Important genetic aberrations include up-regulation of EGFR and MDM2 function and loss of PTEN function in primary glioblastoma, and up-regulation of PDGFRA and CDK4 function in secondary glioblastomas that arise from a pre-existing lower grade astrocytoma. TP53, CDKNA2 and RB1 functions are often lost in secondary glioblastomas. Amplifications of PDGFRA, KIT and VEGFR2 may also have a role in the genesis of some gliomas. The proteins encoded by these genes have become targets for novel therapies, which include specific inhibitors of the EGFR, KIT, and PDGFR receptor tyrosine kinases.