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 hav e been characterized. Based on the genomic map of the 2q break, EST AI46859 5 was positioned near the 2q33 translocation and the full-length gene and c DNA were isolated. This 57-kb gene, designated the DIRC1 gene, was disrupte d between exons 1 and 2 by the familial translocation. The 1.5-kb mRNA enco des an 11-kDa predicted protein of 104 amino acids. Low-level expression of DIRC1 was detected by reverse transcriptase-polymerase chain reaction ampl ification in adult placenta, testis, ovary, and prostate and in fetal kidne y, spleen, and skeletal muscle. A GFP-Dirc1 fusion protein was expressed in vitro and a polyclonal anti-Dirc1 peptide serum was prepared. A panel of c ancer and cancer-derived cell line DNAs was examined for DIRC1 mutations, b ut only a rare polymorphism was observed. Two familial tumors showed loss o f the derivative 3 chromosome, as observed in a Dutch kindred with t(2;3)as sociated renal cancers. Mutations in the second DIRC1 allele were not detec ted. Further studies will be required to determine if disruption of the DIR C1 gene contributed to development of the associated familial clear cell re nal cancers.