Fragile histidine triad gene and skin cancer

Five years ago the fragile histidine triad (FHIT) gene including the most c ommon fragile site locus of the human genome, FRA3B, was identified. The ge ne is altered in many types of cancer and several data support the idea tha t FHIT has to be considered a tumor suppressor. FHIT abnormalities were inv estigated in some skin tumors. Fifty-seven per cent of Merkel cell carcinom as displayed abnormal FHIT products but the involvement of FHIT in human no n-melanoma skin cancer is still unclear. Because the murine Fhit locus is s imilar to its human homologue and is altered in cancer cell lines, we have established a strain of Fhit-deficient mice. After N-nitroso-methylbenzylam ine treatment, the spectrum of tumors developed by the Fhit-deficient mice was similar to those observed in a familial skin cancer condition, the Muir -Torre syndrome, although there is no clear evidence yet for a relationship of FHIT and the human syndrome. Because cancer cells lacking in FHIT are d efective in apoptosis, we propose the Fhit-deficient mouse as a model to un derstand a possible proapoptotic mechanism deficiency in the human syndrome .