Hereditary neurological tumor syndromes: clues to glioma oncogenesis?

The author reviewed five hereditary neurological tumor syndromes associated with gliomas: Li-Fraumeni cancer syndrome, neurofibromatosis type 1 (NF1) and type 2 (NF2), tuberous sclerosis (TS), and Turcot syndrome. In each case, clinical manifestation, genetic localization, and protein function were identified. Correlation with glioma oncogenesis demonstrated the following associations: 1) p53 mutation (Li-Fraumeni) with astrocytoma progression; 2) NF1 mutation (NF1) with pilocytic astrocytomas; and 3) NF2 mutation (NF2) with ependymoma formation. The role of the TS gene and the adenomatous polypopsis coli gene (Turcot syndrome) in glioma oncogenesis is not clear. Because tumorigenesis is a multistep process, it would be premature to equate a specific germline mutation with the multiple somatic mutations required for glioma formation. However, identification of specific germline genetic mutations provides a model for the multiple tumor suppressor genes involved in glioma pathogenesis.