FHIT: from gene discovery to cancer treatment and prevention.
Chromosomal abnormalities, including homozygous deletions and loss of heterozygosity, are among the most common features of human tumours. The short arm of human chromosome 3, particularly the region 3p14.2, is a major site of such rearrangements. The 3p14.2 region spans the most active common fragile site of the human genome, encompassing a familial-kidney-cancer-associated breakpoint and a papilloma virus integration site. 6 years ago, the FHIT gene was identified in this region. Subsequent studies have shown that FHIT is commonly the target of chromosomal aberrations involving the long arm of human chromosome 3 and is thereby inactivated in most of the common human malignant diseases, including cancers of the lung, oesophagus, stomach, breast, and kidney. During the past 5 years, evidence has accumulated in support of a tumour-suppressor function for FHIT. In this review, we describe the recent findings in the molecular biology of FHIT with particular focus on the opportunities for treatment and prevention of cancer that have emerged.
Pekarsky
Yuri
Y
Kimmel Cancer Center, Thomas Jefferson University, PA 19107, USA.
Zanesi
Nicola
N
Palamarchuk
Alexey
A
Huebner
Kay
K
Croce
Carlo M
CM
D017766:Acid Anhydride Hydrolases; D002471:Cell Transformation, Neoplastic; D002869:Chromosome Aberrations; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000503:physiopathology; D027383:Papillomaviridae / Q000472:pathogenicity; D030361:Papillomavirus Infections / Q000150:complications; D014412:Tumor Virus Infections / Q000150:complications; D000099170:Bis(5'-adenosyl)triphosphatase
D017766:Acid Anhydride Hydrolases; D009363:Neoplasm Proteins; D000099170:Bis(5'-adenosyl)triphosphatase