Frequent Breakpoints in the 3p14.2 Fragile Site, FRA3B, in Pancreatic Tumors

FRA3B , at chromosomal band 3p14.2, is the most active common fragile site in the human genome. Homozygous deletions in the region of FRA3B have been observed in many types of solid tumors. Recently, the FHIT gene was reported to span FRA3B and was shown to be homozygously deleted in several gastric and colonic tumor cell lines. Several microsatellite markers that precisely define the 1.0-Mb region surrounding FRA3B and FHIT have been utilized, along with other 3p microsatellites, to analyze the loss of 3p sequences in 25 primary pancreatic adenocarcinomas. The high density of microsatellite markers in the 3p14.2 region enabled us to both identify losses within and flanking FRA3B in pancreatic cancer and define the breakpoints. We observed loss of heterozygosity of 3p14.2 markers in 16 of 25 pancreatic tumors and loss of heterozygosity of 3p markers outside of 3p14.2 in only 2 of 25 tumors of this type. There appears to be a dramatic clustering of chromosomal breakpoints at 3p14.2 in and immediately distal to FRA3B in pancreatic cancer. We detected no homozygous deletions in this region.