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 of cancer. p53 mutations occur frequently in sporadic lymphoma, and, in mice deficient for p53, lymphoma is the most common type of malignancy. Families with an increased incidence of lymphoma have been described, suggesting an inherited predisposition to lymphoma in these circumstances. To determine whether the predisposition to lymphoma in these families 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. However, p53 expression assessed by immunohistochemistry, which suggests mutation, was observed in 35% of the tumor samples from the familial Hodgkin's disease cases and in 13% of the familial non-Hodgkin's lymphoma cases. These results suggest that p53 mutations do not play a critical role in heritable susceptibility to lymphoma. p53 may act by different, non-mutation related mechanisms in this setting, or be involved in late events in the pathogenesis of these tumors.
Weintraub
M
M
Pediatric Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Lin
A Y
AY
Franklin
J
J
Tucker
M A
MA
Magrath
I T
IT
Bhatia
K G
KG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D005091:Exons; D005190:Family; D005260:Female; D015870:Gene Expression; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006689:Hodgkin Disease / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008223:Lymphoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000096:biosynthesis
D016159:Tumor Suppressor Protein p53