MUTATIONS OF THE HUMAN HOMOLOG OF DROSOPHILA PATCHED IN THE NEVOID BASAL-CELL CARCINOMA SYNDROME

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal domin ant disorder characterized by multiple basal cell carcinomas (BCCs), p its of the palms and soles, jaw keratocysts, a variety of other tumors , and developmental abnormalities. NBCCS maps to chromosome 9q22.3. Fa milial and sporadic BCCs display loss of heterozygosity in this region , consistent with the gene being a tumor suppressor. A human sequence (PTC) with strong homology to the Drosophila segment polarity gene, pa tched, was isolated from a YAC and cosmid contig of the NBCCS region. Mutation analysis revealed alterations of PTC in NBCCS patients and in related tumors. We propose that a reduction in expression of the patc hed gene can lead to the developmental abnormalities observed in the s yndrome and that complete loss of patched function contributes to tran sformation of certain cell types.