PTCH2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas

By a combination of cDNA library screening, rapid amplification of cDNA end s analysis, and BAC sequencing, a novel human patched-like gene (PTCH2) has been cloned and sequenced. The genomic organization is similar to PTCH1 wi th 22 exons and, by radiation hybrid mapping, PTCH2 has been localized to c hromosome 1p33-34, a region often lost in a variety of tumors. Several alte rnatively spliced mRNA forms of PTCH2 were identified, including transcript s lacking segments thought to be involved in sonic hedgehog binding and mRN As with differentially defined 3' terminal exons. In situ hybridization rev ealed high expression of PTCH2 transcripts in both familial and sporadic ba sal cell carcinomas in similarity to what has been observed for PTCH1, sugg esting a negative regulation of PTCH2 by PTCH1, This finding tightly links pTCH2 with the sonic hedgehog/PTCH signaling pathway, implying that PTCH2 h as related, but yet distinct, functions than PTCH1.