IDENTIFICATION OF MUTATIONS IN THE HUMAN PATCHED GENE IN SPORADIC BASAL-CELL CARCINOMAS AND IN PATIENTS WITH THE BASAL-CELL NEVUS SYNDROME

Mutations in PATCHED (PTC), the human homolog of the Drosophila patche d gene, have been identified in most exons of the gene in patients wit h the basal cell nevus syndrome and in sporadic basal cell carcinomas. We have screened the 23 PTC exons for mutations using single strand c onformation polymorphism analysis of DNA from 86 basal cell nevus synd rome probands, 26 sporadic basal cell carcinomas, and seven basal cell nevus syndrome-associated basal cell carcinomas. This screen identifi ed mutations located in eight exons in 13 of the basal cell nevus synd rome patients and in three of the tumors. The most common mutations we re frameshifts resulting in premature chain termination. These results provide further evidence for the crucial role of PTC as a tumor suppr essor in human keratinocytes.