ABSENCE OF GERMLINE P53 MUTATIONS IN FAMILIAL LYMPHOMA

p53, a tumor suppressor gene, is frequently mutated in sporadic human cancer, and inherited mutations in p53 predispose to the early onset o f cancer, p53 mutations occur frequently in sporadic lymphoma, and, in mice deficient for p53, lymphoma is the most common type of malignanc y, Families with an increased incidence of lymphoma have been describe d, suggesting an inherited predisposition to lymphoma in these circums tances, To determine whether the predisposition to lymphoma in these f amilies results from germline mutations in p53, we analysed exons 4-11 of the p53 gene in 35 individuals from 19 lymphoma-prone kindreds, We found no germline p53 mutations in any of the individuals tested, How ever, p53 expression assessed by immunohistochemistry, which suggests mutation, was observed in 35% of the tumor samples from the familial H odgkin's disease cases and in 13% of the familial non-Hodgkin's lympho ma cases, These results suggest that p53 mutations do not play a criti cal role in heritable susceptibility to lymphoma, p53 may act by diffe rent, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors.