Common fragile genes and digestive tract cancers.

FRA3B and FRA16D are the most sensitive common chromosomal fragile site loci in the human genome. Two tumor suppressor genes, the fragile histidine triad (FHIT) gene and the WW domain-containing oxidoreductase (WWOX), map to the common fragile sites, FRA3B and FRA16D, respectively. Interestingly, FHIT and WWOX have similarities: for example, they are both larger than 1 Mb and encompass fragile sites, they both show frequent allelic loss regions in various human cancers, they both span a region of homozygous deletion in multiple cancers, and they both frequently show aberrant transcripts. The development of human cancers, including digestive tract cancers, is strongly associated with exposure to environmental carcinogens. Common fragile sites are very sensitive to this type of exposure, and the resulting DNA damage leads to the inactivation of genes such as FHIT and WWOX. We present an overview of these two common fragile genes, namely FHIT/FRA3B and WWOX/FRA16D, in digestive tract cancers.