Abstract: The present invention relates to nucleotide sequences of FHIT genes and amino acid sequences of their encoded proteins, as well as derivatives and analogs thereof, and antibodies thereto. The FHIT gene sequence is mutated in diseases involving cell overproliferation, particularly malignancies of the digestive tract. The present invention further relates to the use of FHIT genes and their encoded proteins as diagnostic and therapeutic reagents for the detection and treatment of disease states associated with cell overproliferation.

Abstract: The invention provides nonhuman transgenic animals with a disrupted FHIT gene. The invention further provides transgenic mice in which one or both Fhit alleles have been inactivated. Preferably, the Fhit-deficient mice develop multiple tumors of both visceral and sebaceous origin, similar to those of Muir-Torre familial cancer syndrome. The present invention further relates to the generation of these transgenic mice and their use as model systems to study the effects of carcinogenic agents in promoting clonal expansion of neoplastic cells in cancers, preferably gastrointestinal cancers of which Muir-Torre syndrome is a subset. The invention further relates to testing therapeutic agents for their efficacy in the prevention and treatment of cancer, preferably gastrointestinal cancer.

Abstract: The present invention relates to nucleotide sequences of FHIT genes and amino acid sequences of their encoded proteins, as well as derivatives and analogs thereof, and antibodies thereto. The FHIT gene sequence is mutated in diseases involving cell overproliferation, particularly malignancies of the digestive tract. The present invention further relates to the use of FHIT genes and their encoded proteins as diagnostic and therapeutic reagents for the detection and treatment of disease states associated with cell overproliferation.