FREQUENT HOMOZYGOUS DELETIONS IN THE FRA3B REGION IN TUMOR-CELL LINESSTILL LEAVE THE FHIT EXONS INTACT

FRA3B at human chromosomal band 3p14.2 is the most active common fragi le site in the human genome. The molecular mechanism of fragility at t his region remains unknown but does not involve expansion of a trinucl eotide or minisatellite repeat as has been observed for several of the cloned rare fragile sites. Deletions and rearrangements at FRA3B have been observed in a number of distinct tumors. The recently identified putative tumor suppressor gene FHIT spans FRA3B, and various groups h ave reported identifying deletions in this gene in different tumors. U sing a high density of PCR amplifiable markers within FRA3B searching for deletions in the FRA3B region, we have analysed 21 tumor cell line s derived from renal cell, pancreatic, and ovarian carcinomas. We foun d a commonly deleted region in the renal cell and ovarian carcinoma ce ll lines located in the middle of an HPV16 viral integration site. Des pite the presence of deletions in the FRA3B region in most of the cell lines, we did not detect alterations in FHIT exons in any of the cell lines examined. Thus, deletions of 3p14.2 in these carcinoma cell lin es may simply reflect instability of the FRA3B region during tumor pro gression.