biostudies-literatureGemmill RMNCI NIH HHS9572-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC21380biostudies-literatureUnknown95(16)The 3;8 chromosomal translocation, t(3;8)(p14.2;q24.1), was described in a family with classical features of hereditary renal cell carcinoma. Previous studies demonstrated that the 3p14.2 breakpoint interrupts the fragile histidine triad gene (FHIT) in its 5' noncoding region. However, evidence that FHIT is causally related to renal or other malignancies is controversial. We now show that the 8q24.1 breakpoint region encodes a 664-aa multiple membrane spanning protein, TRC8, with similarity to the hereditary basal cell carcinoma/segment polarity gene, patched. This similarity involves two regions of patched, the putative sterol-sensing domain and the second extracellular loop that participates in the binding of sonic hedgehog. In the 3;8 translocation, TRC8 is fused to FHIT and is disrupteProceedings of the National Academy of Sciences of the United States of AmericaThe hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8.PMC21380CA58187Boldog FGemmill RMRobinson LJLi FDrabkin HATanaka NWest JDSmith DIfalseThe hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8.The 3;8 chromosomal translocation, t(3;8)(p14.2;q24.1), was described in a family with classical features of hereditary renal cell carcinoma. Previous studies demonstrated that the 3p14.2 breakpoint interrupts the fragile histidine triad gene (FHIT) in its 5' noncoding region. However, evidence that FHIT is causally related to renal or other malignancies is controversial. We now show that the 8q24.1 breakpoint region encodes a 664-aa multiple membrane spanning protein, TRC8, with similarity to the hereditary basal cell carcinoma/segment polarity gene, patched. This similarity involves two regions of patched, the putative sterol-sensing domain and the second extracellular loop that participates in the binding of sonic hedgehog. In the 3;8 translocation, TRC8 is fused to FHIT and is disrupte1998-01-01T00:00:00Z1998 Aug2025-04-04T08:59:09.788Z2019-03-27T00:17:48ZS-EPMC21380968912210.1073/pnas.95.16.9572