THE MURINE FHIT GENE IS HIGHLY SIMILAR TO ITS HUMAN ORTHOLOGUE AND MAPS TO A COMMON FRAGILE SITE REGION

The human FHIT gene is a putative tumor suppressor gene that maps to h uman chromosome band 3p14,2 in a region that is frequently deleted in cancers, It exhibits both genomic deletions and aberrant transcripts i n a variety of tumors and spans the common fragile site FRA3B, This fr agile site extends over a broad region of several hundred kb within th e FHIT gene and may account for its instability in tumors. As one test of this hypothesis, we isolated the murine Fhit gene and asked whethe r it also contains a common fragile site and if it is unstable in mous e tumors or tumor cell lines. The Fhit gene was isolated, and the sequ ence was found to be 87.5% identical to that of the human FHIT gene in the open reading frame. Using fluorescence in situ hybridization, Fhi t was assigned to mouse chromosome band 14A2, in a region that was pre viously shown to contain an aphidicolin-inducible mouse fragile site. Fluorescence ill situ hybridization with genomic clones containing Fhi t and flanking sequences demonstrated that gaps and breaks in the frag ile site occur over a broad region within and proximal to the Fhit loc us. Thus, the physical relationship of Fhit to a common fragile site i s similar to that observed with the orthologous human FHIT gene and FR A3B.