FREQUENT BREAKPOINTS IN THE REGION SURROUNDING FRA3B IN SPORADIC RENAL-CELL CARCINOMAS

The constitutive fragile site at chromosomal band 3p14.2, FRA3B, is th e most active common fragile site in the human genome, We have localiz ed aphidicolin-induced breakpoints to two distinct clusters, separated by 200 Kb, in FRA3B (Paradee et al., 1996). Sequence analysis of thes e regions identified two polymorphic microsatellite markers immediatel y adjacent to each of these breakpoint clusters. In this report we hav e used these two new microsatellites and 14 additional 3p microsatelli tes to analyse chromosome 3p breakage and loss in 94 sporadic RCC samp les, including nonpapillary, papillary and oncocytomas, We have found heterozygous loss of 3p14 sequences in >60% of the RCC samples, includ ing both clear cell and papillary renal cell carcinomas, We have found frequent breakage in the region immediately surrounding FRA3B, demons trating that FRA3B does play a role in chromosome breakage and loss in RCC, In contrast to other reports, >50% of the papillary tumors also showed LOH of 3p markers, We also observed microsatellite instability (MIN) with most of the tested markers in seven of eight oncocytomas an d one of 69 clear cell carcinomas, The MIN in some oncocytomas was of the RER + (replication error) type I phenotype, None of the five 3p14. 2 markers detected any homozygous deletions in tumor samples, but 69/9 4 (73%) of the tumors had LOH for the region, which includes the recen tly identified FHIT gene.