MEDULLOBLASTOMAS OF THE DESMOPLASTIC VARIANT CARRY MUTATIONS OF THE HUMAN HOMOLOG OF DROSOPHILA PATCHED

Inactivating mutations in the PTCH gene, a human homologue of the Dros ophila segment polarity gene patched, have been identified recently in patients with nevoid basal cell carcinoma syndrome, These patients ar e predisposed to various neoplasias including basal cell carcinomas an d medulloblastomas (MBs), To determine the involvement of PTCH in spor adic MBs, which represent the most frequent malignant brain tumors in children, we screened for PTCH alterations in an unselected panel of 6 4 biopsy samples from 62 patients and four continuous MB cell lines, a ll derived from patients with sporadic MBs. Using single-strand confor mational polymorphism analysis, we screened exons 2-22 and detected no nconservative PTCH mutations in 3 of 11 samples from sporadic cases of the desmoplastic variant of MB but none in 57 MBs with classical (non -desmoplastic) histology, In two of the tumors with mutations and in t wo additional desmoplastic cases, loss of heterozygosity was found at 9q22, These findings suggest that PTCH represents a tumor suppressor g ene involved in the development of the desmoplastic variant of MB.