Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system

摘要: The human homologue of the Drosophila segment polarity gene patched (PTCH) has recently been identified as tumor suppressor responsible for nevoid basal cell carcinoma (BCC) syndrome (H. Hahn et al., Cell, 85: 841-851, 1996; R. L. Johnson Science (Washington DC), 272: 1668-1671, 1996). In addition to multiple BCCs, patients with BCC have a predisposition development primitive neuroectodermal tumors (PNETs) central nervous system. We analyzed 9 sporadic BCCs and 37 PNETs mutation expression PTCH gene. mutations were found in 3 (33.3%) 5 (14%), including 1 cerebral PNETs, 2 15 medulloblastomas, 17 desmoplastic medulloblastomas. sequence changes six these (four two BCCs) predicted result truncated proteins. Missense detected one PNET each. addition, novel polymorphisms exon 2, intron 5, 10, 14 PTCH. Reverse transcription-PCR analysis revealed increased levels compared nonneoplastic brain tissue normal skin majority investigated. Our data suggest that genetic alterations are not only significance hereditary but also involved molecular pathogenesis subset system PNETs.