Polymorphic variation at the BAT-25 and BAT-26 loci in individuals of African origin - Implications for microsatellite instability testing

Instability in the repeat size of microsatellite sequences has been describ ed in both hereditary nonpolyposis and sporadic colorectal cancers. Tumors expressing microsatellite instability are identified through the comparison of the repeat sizes at multiple microsatellite loci between tumor and matc hed normal tissue DNA. The use of a five-marker panel including two mononuc leotide repeat microsatellites, BAT-25 and BAT-26, has recently been sugges ted for the clinical determination of tumor microsatellite instability. The BAT-25 and BAT-26 loci included in this panel have both demonstrated sensi tivity to microsatellite instability and normal quasimonomorphic allelic pa tterns, which has simplified the distinction between normal and unstable al leles, However, in this study, we identified allelic variations in the size of the poly(A) tract at BAT-26 in 12.6% of 103 healthy African-Americans s creened. In addition, 18.4% exhibited allelic size variations in the poly(T ) tract at BAT-25. Finally, 2.9% showed variant alleles at both BAT-25 and BAT-26 loci. Screening a small population of Nigerians confirmed the polymo rphic nature of both loci and the ethnic origin of alleles not identified i n other populations studied thus far. Our results dispute the quasimonomorp hic nature of both BAT-25 and BAT-26 in all populations and support the nee d for thorough population studies to define the different allelic profiles and frequencies at microsatellite loci.