GENETICS AND MOLECULAR-BIOLOGY OF NEURINOMAS AND MENINGIOMAS

Tumorigenesis is caused by abnormal proliferation of cells that escape regulatory mechanisms. Most of the molecular events leading to the formation of tumors are still largely unknown. In this paper, experimental data supporting a causative role for cellular genes, termed oncogenes, in the formation of tumors of the nervous system are reviewed. Two types of oncogenes are described: dominant oncogenes, characterized by the fact that one abnormal copy of the gene is sufficient to induce tumorigenesis, and recessive oncogenes which require the inactivation of both copies of the gene to lead to tumor formation. The role of recessive oncogenes in tumorigenesis of the nervous system is illustrated by molecular studies of meningiomas and neurinomas. The mutation of one, and perhaps two loci on chromosome 22, has indeed been shown to be most probably the causative molecular event in the growth of these two tumors when they occur either in their sporadic form, or in neurofibromatosis type 2. All the available data support the proposition of systematically analyzing a large number of tumors to eventually correlate clinical phenotype and evolution, to the genetic abnormalities observed. Furthermore, the understanding of the normal and pathological function of oncogenes should lead to future therapeutical improvements.