FRA7G extends over a broad region: coincidence of human endogenous retroviral sequences (HERV-H) and small polydispersed circular DNAs (spcDNA) and fragile sites

Abstract

FRA7G is an aphidicolin-inducible common fragile site at human chromosomal band 7q31.2. This region is frequently altered in a number of different tumor types including prostate, breast, and ovarian cancer. It has also been hypothesized that this region contains an important tumor suppressor gene which is mutated during the development of these cancers or an oncogene which is amplified. We previously used a FISH-based approach to isolate YAC clones which spanned FRA7G. In this report, we describe the isolation and restriction endonuclease mapping of three overlapping P1 clones which cover FRA7G and the region frequently altered in the different cancers. FISH-based analysis of these clones reveals that aphidicolin-induced breakage in the FRA7G region occurs over a region of at least 300 Kb in length. We have also localized a previously sequenced BAC clone to this region. The sequence obtained from this clone reveals the presence of an endogenous retroviral sequence (HERV-H) in the midst of the FRA7G region as well as sequences with homology to small polydispersed circular DNAs (spcDNAs). Thus for the first two cloned common fragile sites, FRA7G and FRA3B, there is an association with both spcDNAs and hot-spots for viral integration.