Exclusion of a p53 germline mutation in a classic Li-Fraumeni syndrome family

• Published in: Human genetics 1998-06, Vol.102 (6), p.681-686
• Main Authors: EVANS, S. C, MIMS, B, MCMASTERS, K. M, FOSTER, C. J, DEANDRADE, M, AMOS, C. I, STRONG, L. C, LOZANO, G
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Biological and medical sciences; Complex syndromes; Female; Genes, p53; Genetic Linkage; Germ-Line Mutation; Humans; Li-Fraumeni Syndrome - genetics; Male; Medical genetics; Medical sciences; Mutation; Pedigree; Polymorphism, Single-Stranded Conformational; Saccharomyces cerevisiae - genetics
• ISSN: 0340-6717; 1432-1203
• DOI: 10.1007/s004390050761

Li-Fraumeni syndrome (LFS) is characterized by a high risk of sarcomas, early onset of breast cancer, and a diversity of other cancers occurring as multiple primary tumors in multiple family members. In many families with LFS, germline mutations within the tumor-suppressor gene p53 have been identified. However, mutations in p53 have not been detected in approximately 30% of LFS families. To address the possibility either that p53 mutations were being missed or that another predisposing gene is altered in LFS, we used a variety of methods to accurately determine the p53 status in a large LFS kindred. A transcriptional activation assay on exons 4-10 of p53 excluded a mutation within the DNA-binding domain of p53. Single-stranded conformational-polymorphism analysis, using intronic primers and sequencing of all the coding exons and intron/exon junctions, also yielded no mutations. Finally, linkage analysis excluded potential mutations in the noncoding regions of p53. Our findings exclude the presence of a p53 germline mutation in a classic LFS family.