FHIT alterations in breast cancer

The FHIT gene encodes a diadenosine hydrolase and may be involved in growth control pathways of the cell. Studies on protein-protein interactions, cell lines, including tumourigenicity tests, and knockout mice suggest that the Fhit protein is involved in cell proliferation and apoptosis, and might act as a tumour suppressor. In several different cancers, including breast cancer, alterations in the FHIT gene have been detected in high frequency. The most common alterations are: deletions, DNA hypermethylation, abnormal transcripts and reduced expression at RNA and protein level. The FHIT gene is located at the FRA3B fragile site at chromosome 3p14.2, and alterations in the FHIT gene and Fhit protein have been found associated with genome instability, particularly in BRCA2 mutated breast tumours. This paper will focus on some of the functional aspects of the Fhit protein with respect to tumour pathogenesis and on aberrations detected in breast cancer.