Common fragile sites and cancer (review)

Abstract

Chromosomal fragile sites are specific loci which are especially susceptible to forming gaps, breaks and rearrangements in metaphase chromosomes when cells are cultured under conditions that inhibit DNA replication. Fragile sites are grouped into two classes the 'rare' and the 'common' fragile sites, based on their frequency of occurrence and means of induction. The common fragile sites are apparently present as a constant feature in all individuals and their clinical significance is that they might predispose chromosomes to breakage and rearrangement during cancer development. The most frequently observed common fragile sites occur, in decreasing order, at 3p14.2 (FRA3B), 16q23 (FRA16D), 6q26 (FRA6E), 7q32 (FRA7H), and Xp22 (FRAXB). FRA3B has been of particular interest since it is the most active common fragile site, and is located in a chromosomal band that is frequently deleted in several solid tumors suggesting that a putative tumor suppressor gene resides there. In this review we describe our work on the characterization of FRA3B and the analysis of deletions in the FRA3B region in several different tumor-derived cell lines. We also describe our efforts to identify other common fragile sites and to determine the role that these sites play in tumor development.