FHIT GENE AND THE FRA3B REGION ARE NOT INVOLVED IN THE GENETICS OF RENAL-CELL CARCINOMAS

The FHIT gene locus at 3p14.2 covers about 500 kb, including the fragi le site FRA3B and the constitutional t(3;8) breakpoint associated with the development of multiple renal cell carcinomas (RCC). A terminal d eletion of the short arm of chromosome 3 with the most distal breakpoi nt in the FRA3B region is the characteristic genetic event in nonpapil lary RCC. Since aberrant FHIT transcripts have been observed in gastro intestinal and other tumors, this gene has been suggested to function as a tumor suppressor. To evaluate the role of FHIT and the FRA3B regi on in the genetics of RCC, we analyzed FHIT expression by RT-PCR and p erformed microsatellite deletion mapping in the FHIT region. In additi on to two cases from a t(3;8) family, only three out of 100 sporadic n onpapillary RCC showed a breakpoint within the FHIT region, whereas 94 tumors showed a deletion breakpoint proximal to the FHIT gene. FHIT t ranscripts of normal size were observed in 33 out of 34 tumors. Direct sequencing of eight PCR products revealed a normal FHIT sequence with out mutations in the coding region. An established cell line from a re nal cancer xenograft showed a smaller FHIT transcript, Sequence analys is revealed a mixture of several splicing variants of the FHIT gene. S ince only three out of 100 sporadic nonpapillary RCC had a deletion br eakpoint within the FRA3B/FHIT region, and since all but one renal cel l tumor showed a normal FHIT transcript, we can exclude the involvemen t of the FHIT gene and the FRA3B region in the genetics of renal cell cancer. (C) 1997 Wiley-Liss, Inc.