MOLECULAR CHARACTERIZATION OF HUMAN COMMON FRAGILE SITE FRA6E, A LARGE GENOMIC REGION SPANNING 9 Mb

Common fragile sites of the human genome are suggested to be potentially involved in cancer development; FRA6E (6q26), one of the most frequently expressed common fragile sites in humans, is located in a region frequently found rearranged in cancer. We have mapped FRA6E by FISH analysis with YAC, BAC and PAC genomic clones, and have characterized the fragility of the region by sequence analysis. Recent published data indicated that the location of FRA6E is about 2.5 Mb beyond the telomeric side of the region considered in the present study. Taken together, our data and previously reported data indicate that FRA6E spans approximately 9 Mb, corresponding to a chromosomal region located at 6q25.3-6q26. It has been recently suggested that unusual structural features, detected as high flexibility motives by sequence analysis, are overrepresented within fragile sites, and that this organization can be relevant for the intrinsic fragility of these regions. We have carried out a search for fragility motives within the genomic sequence corresponding to FRA6E, confirming the significance of unusual structural organization of chromosome sequences with respect to the location of common fragile sites. A number of expressed genes map at FRA6E, which can be relevant for cancer. RT-PCR analysis revealed that some of them are down-regulated in melanoma tumors. The results outlined in this study underline the need for a deep investigation of the fragility regions of the human genome, which are probably wider than previously thought.