Characterization of the human Rad51 genomic locus and examination of tumors with 15q14-15 loss of heterozygosity (LOH)

Human Rad51 (hRad51) has been found to be associated with BRCA1, BRCA2, and p53 either directly or indirectly and is one of at least eight human genes that are members of the Escherichia coli RecA/Saccharomyces, cerevisiae Ra d51 family thought to affect genomic stability through DNA recombination/re pair processes. While inactivation of DNA mismatch repair clearly leads to instability of repeated sequences and to an increased risk for tumorigenesi s, such a parallel for the RecA family members has not been reported. Recen tly, a high frequency of loss of heterozygosity at chromosome 15q14-15, nea r the genomic region containing hRad51, has been reported in human tumors ( W. Wick et al., Oncogene, 12: 973-978, 1996). To determine whether hRad51 i nactivation may be involved in the etiology of these tumors, we have charac terized the hRad51 genetic locus and mapped it to chromosome 15q14-15 withi n the central region of loss of heterozygosity. However, single-strand conf ormational polymorphism analysis and direct sequencing of tumors did not re veal any mutations in the hRad51 coding sequence or intron/exon boundaries. We also examined the DNA methylation status of a CpG-rich region in the pu tative hRad51 promoter region. No indication of hypermethylation was found. These results suggest that hRad51 is not a tumor suppressor because it is either an essential gene, redundant gene and/or independent of the BRCA1/BR CA2 tumor suppressor pathway(s).