TP53 mutation and haplotype analysis of two large African American families

Hum Mutat. 1999;14(3):216-21. doi: 10.1002/(SICI)1098-1004(1999)14:3<216::AID-HUMU4>3.0.CO;2-X.


Two large apparently unrelated African American families with a high incidence of breast cancer and other tumors characteristic of Li-Fraumeni breast sarcoma cancer family syndrome were studied. Mutation screening revealed that in both families the affected members carried a germline mutation of the TP53 gene at codon 133 (ATG--> ACG, M133T). In order to determine whether an ancestral haplotype was shared by these two families, polymorphic markers within and flanking the TP53 gene were studied. Haplotype analysis using five markers revealed an identical haplotype shared by the two families. Loss of heterozygosity at the TP53 locus in the probands' tumor tissues from each family was observed; in each case, the retained allele carried the common haplotype. The frequency of this haplotype in the general African American population is <0.003. This unique haplotype, combined with the rare TP53 mutation, suggests that these African American families share a common ancestry. This finding suggests that other African Americans may be carriers of this mutation and thus may be at risk of early-onset breast cancer or other cancers characteristic of the Li-Fraumeni breast sarcoma cancer family syndrome. The finding of recurring mutations in African Americans may facilitate carrier screening and identification in this population.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Breast Neoplasms / genetics
  • DNA Mutational Analysis
  • Female
  • Gene Frequency
  • Genes, p53 / genetics*
  • Haplotypes / genetics*
  • Humans
  • Li-Fraumeni Syndrome / genetics
  • Loss of Heterozygosity
  • Male
  • Mutation
  • Pedigree
  • Polymorphism, Single-Stranded Conformational