[Tumor suppressor gen mutation in the germ line: its significance in familial and sporadic tumors].

Since the discovery of the retinoblastoma tumor suppressor gene many others have been described associated with a variety of different familial syndromes. These include the Li-Fraumeni syndrome, familial breast/ovarian cancer, multiple endocrine neoplasia (MEN1), neurofibromatosis 1 and 2, tuberous sclerosis and von Hippel-Lindau disease. Persons harboring a germ line mutation in a tumor suppressor gene are not born with disease, merely the predisposition to develop one. This is due to the fact that they have inherited only one functional copy compared to persons with no predisposition who have two copies. Germ line mutations have not to be inherited, they can result from a spontaneous mutation occurring during gametogenesis in one patient. Persons with an inherited or de-novo germ line mutation have similar risks to develop multiple cancer or to transmit the defective gene to their offspring. The genes can be analyzed by molecular genetic techniques allowing for a precise genetic diagnosis as well as reliable genetic counselling.