REFINING A PROXIMAL BREAKPOINT CLUSTER AT CHROMOSOME 3P11.2 IN NON-PAPILLARY RENAL-CELL CARCINOMAS

Our previous cytogenetic and microsatellite analyses showed a terminal deletion of chromosome 3p segments with a breakpoint region between 3 p11.2 and 3p14.1 bands in 98% of non-papillary renal cell carcinomas ( RCC). This breakpoint region covers approx. 20-25 cM genetic distance. Earlier, we found a higher frequency of rearrangements at chromosome 3p11.2 and have therefore now analyzed 14 sporadic and 26 VHL-associat ed RCCs with 6 polymorphic microsatellite markers mapped to this regio n. Thirty-three per cent of the breakpoints were mapped to a genetic d istance of less than one-twentieth of the large breakpoint region 3p11 .2-14.1. We suggest that unstable DNA sequences at chromosome 3p11.2 s erve as a genetic basis for deletions and homologous and non-homologou s recombinations to remove distal 3p sequences with one copy of RCC ge ne(s) in different types of tumors. We have identified a YAC clone 909 d5 that spans the most frequently occurring breaks between loci D3SI2I , D3S1101, and D3S1552 and allows this region to be cloned. (C) 1996 W iley-Liss, Inc.