TP53 mutation and haplotype analysis of two large African American families

Two large apparently unrelated African American families with a high incide nce of breast cancer and other tumors characteristic of Li-Fraumeni breast sarcoma cancer family syndrome were studied. Mutation screening revealed th at 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 marke rs within and flanking the TP53 gene were studied, Haplotype analysis using five markers revealed an identical haplotype shared by the two families. L oss of heterozygosity at the TP53 locus in the probands' tumor tissues from each family was observed; in each case, the retained allele carried the co mmon haplotype. The frequency of this haplotype in the general African Amer ican population is <0.003, This unique haplotype, combined with the rare TP 53 mutation, suggests that these African American families share a common a ncestry. 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 o ther cancers characteristic of the Li-Fraumeni breast sarcoma cancer family syndrome, The finding of recurring mutations in African Americans may faci litiate carrier screening and identification in this population. Hum Mutat 14:216-221, 1999. (C) 1999 Wiley-Liss, Inc.