title: Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched.
abstract: Inactivating mutations in the PTCH gene, a human homologue of the Drosophila segment polarity gene patched, have been identified recently in patients with nevoid basal cell carcinoma syndrome. These patients are predisposed to various neoplasias including basal cell carcinomas and medulloblastomas (MBs). To determine the involvement of PTCH in sporadic MBs, which represent the most frequent malignant brain tumors in children, we screened for PTCH alterations in an unselected panel of 64 biopsy samples from 62 patients and four continuous MB cell lines, all derived from patients with sporadic MBs. Using single-strand conformational polymorphism analysis, we screened exons 2-22 and detected nonconservative PTCH mutations in 3 of 11 samples from sporadic cases of the desmoplastic variant of MB but none in 57 MBs with classical (nondesmoplastic) histology. In two of the tumors with mutations and in two additional desmoplastic cases, loss of heterozygosity was found at 9q22. These findings suggest that PTCH represents a tumor suppressor gene involved in the development of the desmoplastic variant of MB.
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Germany. pietsch-t@uni-bonn.de
authors.forename: T
authors.initials: T
authors.lastname: Pietsch
authors.forename: A
authors.initials: A
authors.lastname: Waha
authors.forename: A
authors.initials: A
authors.lastname: Koch
authors.forename: J
authors.initials: J
authors.lastname: Kraus
authors.forename: S
authors.initials: S
authors.lastname: Albrecht
authors.forename: J
authors.initials: J
authors.lastname: Tonn
authors.forename: N
authors.initials: N
authors.lastname: Sörensen
authors.forename: F
authors.initials: F
authors.lastname: Berthold
authors.forename: B
authors.initials: B
authors.lastname: Henk
authors.forename: N
authors.initials: N
authors.lastname: Schmandt
authors.forename: H K
authors.initials: HK
authors.lastname: Wolf
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
authors.forename: B
authors.initials: B
authors.lastname: Wainwright
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: O D
authors.initials: OD
authors.lastname: Wiestler
authors.forename: C
authors.initials: C
authors.lastname: Wicking
mesh_terms: D000293:Adolescent; D000818:Animals; D002528:Cerebellar Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D018807:Polymorphism, Single-Stranded Conformational; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011956:Receptors, Cell Surface; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
chemical_list: D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D012333:RNA, Messenger; D011956:Receptors, Cell Surface