Frequent germline deletion polymorphism of chromosomal region 8p12-p21 identified as a recurrent homozygous deletion in human tumors

A number of carcinomas show high frequency of loss of heterozygosity (LOH) at chromosome 8p, suggesting that putative tumor suppressor genes are prese nt in this region. While searching for homozygous deletions in a panel of p ancreatic and biliary tumors, we discovered a homozygous deletion at the mi crosatellite AFMa224wh5 in chromosome region 8p12-p21. We applied a six-ste p algorithm comprising germline analysis, breakpoint sequencing, population screening, online gene mapping, allelic discrimination of tumor-associated Loll, and family history analysis. The results indicated that the deletion was likely due to a normal 102-bp deletion polymorphism present in nearly 10% of the study population, not likely to involve a recessive cancer-assoc iated gene. Researchers need to be aware that germline insertion/deletion p olymorphisms can affect the results of positional cloning efforts in human neoplasms. This problem would be accentuated in studies of cell lines where a paired sample of constitutional DNA is often unavailable. (C) 2001 Acade mic Press.