THE T(X-L)(P11.2-Q21.2) TRANSLOCATION IN PAPILLARY RENAL-CELL CARCINOMA FUSES A NOVEL GENE PRCC TO THE TFE3 TRANSCRIPTION FACTOR GENE

The specific chromosomal translocation t(X;1)(p11,2;q21,2) has been ob served in human papillary renal cell carcinomas, In this study we demo nstrated that this translocation results in the fusion of a novel gene designated PRCC at 1q21,2 to the TFE3 gene at Xp11,2, TFE3 encodes a member of the basic helix-loop-helix (bHLH) family of transcription fa ctors originally identified by its ability to bind to mu E3 elements i n the immunoglobin heavy chain intronic enhancer, The translocation is predicted to result in the fusion of the N-terminal region of the PRO C protein, which includes a proline-rich domain, to the entire TFE3 pr otein, Notably the generation of the chimaeric PRCC-TFE3 gene appears to be accompanied by complete loss of normal TFE3 transcripts, This wo rk establishes that the disruption of transcriptional control by chrom osomal translocation is important in the development of kidney carcino ma in addition to its previously established role in the aetiology of sarcomas and leukaemias.