title: Three germline mutations in the TP53 gene.
abstract: Three germline mutations in the TP53 tumor-suppressor gene are reported, two of which are not reported previously. A missense mutation at codon 265 of TP53 was found in three patients of a family that complied with the definition of the Li-Fraumeni syndrome. A nonsense mutation in 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-Fraumeni-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 missense mutation in codon 235 in a woman diagnosed with breast cancer at age 26 and a recurrence 4 years later. The recurrence, but not the primary tumor, showed an additional missense mutation at codon 245 as well as loss of the wild-type allele. This suggests that the 245 mutation was particularly important for tumor progression and that there might exist heterogeneity in terms of cancer predisposition potential among the various germline TP53 mutations.
authors.affiliation: Department of Human Genetics, University of Leiden, The Netherlands.
authors.forename: R S
authors.initials: RS
authors.lastname: Cornelis
authors.forename: M
authors.initials: M
authors.lastname: van Vliet
authors.forename: M J
authors.initials: MJ
authors.lastname: van de Vijver
authors.forename: H F
authors.initials: HF
authors.lastname: Vasen
authors.forename: P A
authors.initials: PA
authors.lastname: Voute
authors.forename: B
authors.initials: B
authors.lastname: Top
authors.forename: P M
authors.initials: PM
authors.lastname: Khan
authors.forename: P
authors.initials: P
authors.lastname: Devilee
authors.forename: C J
authors.initials: CJ
authors.lastname: Cornelisse
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002469:Cell Separation; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D016158:Genes, p53 / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000473:pathology; D008297:Male; D010375:Pedigree; D011110:Polymorphism, Genetic; D012208:Rhabdomyosarcoma / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D004247:DNA