Integrated analysis of <i>FHIT</i> gene alterations in cancer

The Fragile Histidine Triad Diadenosine Triphosphatase (<i>FHIT</i>) gene is located in the Common Fragile Site FRA3B and encodes an enzyme that hydrolyzes the dinucleotide Ap3A. Although <i>FHIT</i> loss is one of the most frequent copy number alterations in cancer, its relevance for cancer initiation and progression remains unclear. <i>FHIT</i> is frequently lost in cancers from the digestive tract, which is compatible with being a cancer driver event in these tissues. However, <i>FHIT</i> loss could also be a passenger event due to the inherent fragility of the FRA3B locus. Moreover, the physiological relevance of FHIT enzymatic activity and the levels of Ap3A is largely unclear. We have conducted here a systematic pan-cancer analysis of <i>FHIT</i> status in connection with other mutations and phenotypic alterations, and we have critically discussed our findings in connection with the literature to provide an overall view of FHIT implications in cancer.