Genetic markers and animal models of neurocristopathy.

Neurocristopathy is the disorder in which the series of cell and tissue derived from the neural crest are affected. A variety of neural crest tumors, and systemic neurocristopathies such as neurofibromatosis type 1 (NF1) and type 2 (NF2), multiple endocrine neoplasia type 2 (MEN2) and dysplastic nevus syndrome are included in this category. Genetic abnormalities of specific proto-oncogenes and tumor suppressor genes have been discovered in the neurocristopathies. The NF1 gene has GTP-ase activating protein activity, regulates ras pathway and acts as a potential tumor suppressor. The NF2 gene, which is also considered as a tumor suppressor of Schwann cell and meningocyte, has a unique character that it is a linker between adhesion molecule and cytoskeletal protein. Ret proto-oncogene has been proven to be the responsible gene not only of MEN2A but also of MEN2B, familial medullary carcinoma and Hirschsprung disease. Recent progress of positional cloning technique further revealed that p16 gene which is an inhibitor of cycline-dependent kinase is the gene for some of familial malignant melanoma/dysplastic nervus syndrome and sporadic melanoma. ENU-induced rodent model for human Schwann cell tumor and fish model for malignant melanoma have provided useful insights to molecular mechanisms of neural crest tumors. Moreover, introduction of transgenic and gene targeted mouse models for neurocristopathies has made great progress in understanding of the genetic functions in tumoriginesis.