The DIRC1 gene at chromosome 2q33 spans a familial RCC-associated t(2;3)(q33;q21) chromosome translocation.

A reciprocal, balanced, constitutional chromosome translocation, t(2;3)(q33;q21), which is associated with familial clear cell renal cancer, has been described and the genomic regions surrounding the 2q and 3q breakpoints have been characterized. Based on the genomic map of the 2q break, EST AI468595 was positioned near the 2q33 translocation and the full-length gene and cDNA were isolated. This 57-kb gene, designated the DIRC1 gene, was disrupted between exons 1 and 2 by the familial translocation. The 1.5-kb mRNA encodes an 11-kDa predicted protein of 104 amino acids. Low-level expression of DIRC1 was detected by reverse transcriptase-polymerase chain reaction amplification in adult placenta, testis, ovary, and prostate and in fetal kidney, spleen, and skeletal muscle. A GFP-Dirc1 fusion protein was expressed in vitro and a polyclonal anti-Dircl peptide serum was prepared. A panel of cancer and cancer-derived cell line DNAs was examined for DIRC1 mutations, but only a rare polymorphism was observed. Two familial tumors showed loss of the derivative 3 chromosome, as observed in a Dutch kindred with t(2;3)associated renal cancers. Mutations in the second DIRC1 allele were not detected. Further studies will be required to determine if disruption of the DIRC1 gene contributed to development of the associated familial clear cell renal cancers.