INHERITABLE P53 MUTATION IN A PATIENT WITH MULTIPLE CANCER AND ITS SIGNIFICATION FOR GENETIC-COUNSELING

We describe molecular genetic findings in a patient who initially pres ented with an intermediate teratoma of the testis and who many years l ater presented with an oligodendroastrocytoma. In addition he develope d a malignant histiocytoma over the scapula, an adenocarcinoma of the stomach and a late stage adenoma of the sigmoid colon. Due to the deve lopment of several neoplasms the possibility of either ataxia telangie ctasia or Li-Fraumeni syndrome was considered in differential diagnosi s. A molecular genetic investigation revealed that both he and his bro ther carried a germline p53 tumor suppressor gene mutation at codon 24 8. From this result we conclude that this family belongs to the Li-Fra umeni syndrome. Once characterized as belonging to the Li-Fraumeni syn drome, the remaining members of the family were typed to determine if they too carried the same mutation. The two children of the index pati ent were shown not to carry the mutation and are therefore at no incre ased risk of developing any of the Li-Fraumeni spectrum of malignancie s. A molecular genetic investigation into similar families could help to prevent the development of additional malignancies as seen in the i ndex patient, as radiotherapy may interfere with the normal function o f the p53 protein and this may in turn help to orchestrate DNA repair after radiation.