Exclusion of a p53 germline mutation in a classic Li-Fraumeni syndrome family.
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.
Evans
S C
SC
Department of Molecular Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, USA.
Mims
B
B
McMasters
K M
KM
Foster
C J
CJ
deAndrade
M
M
Amos
C I
CI
Strong
L C
LC
Lozano
G
G
D000328:Adult; D000483:Alleles; D005260:Female; D016158:Genes, p53; D008040:Genetic Linkage; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D012441:Saccharomyces cerevisiae / Q000235:genetics