Isolation and characterization of human Patched 2 (PTCH2), a putative tumour suppressor gene in basal cell carcinoma and medulloblastoma on chromosome 1p32

mutations of the human Patched gene (PTCH) have been identified in individu als with the nevoid basal cell carcinoma syndrome (NBCCS) as well as in spo radic basal cell carcinomas and medulloblastomas, We have isolated a homolo gue of this tumour suppressor gene and localized it to the short arm of chr omosome 1 (1p32.1-32.3). Patched 2(PTCH2) comprises 22 coding exons and spa ns similar to 15 kb of genomic DNA, The gene encodes a 1203 amino acid puta tive transmembrane protein which is highly homologous to the PTCH product. We have characterized the genomic structure of PTCH2 and have used single-s tranded conformational polymorphism analysis to search for mutations in PTC H2 in NBCCS patients, basal cell carcinomas and in medulloblastomas, To dat e, we have identified one truncating mutation in a medulloblastoma and a ch ange in a splice donor site in a basal cell carcinoma, suggesting that the gene plays a role in the development of some tumours.