3 GERMLINE MUTATIONS IN THE TP53 GENE

Three germline mutations in the TP53 tumor suppressor gene are reporte d, two of which are not reported previously. A missense mutation at co don 265 of TP53 was found in three patients of a family that complied with the definition of the Li-Fraumeni syndrome. A nonsense mutation i n codon 306 was found in a woman who had had a rhabdomyosarcoma at age 4 and a subsequent breast cancer at age 22. She was part of a Li-Frau meni-like family, but the parental origin of the mutation could not be traced. Finally, while screening for somatic alterations in TP53 in a series of 141 sporadic breast tumors, we detected a constitutional mi ssense mutation in codon 235 in a woman diagnosed with breast cancer a t age 26 and a recurrence 4 years later, The recurrence, but not the p rimary tumor, showed an additional missense mutation at codon 245 as w ell as loss of the wild-type allele. This suggests that the 245 mutati on was particularly important for tumor progression and that there mig ht exist heterogeneity in terms of cancer predisposition potential amo ng the various germline TP53 mutations. (C) 1997 Wiley-Liss, Inc.