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Medulloblastomas of the Desmoplastic Variant Carry Mutations of the Human Homologue of Drosophila patched¹

Department of Neuropathology, University of Bonn Medical Center, Sigmund-Freud-Strasse 25, D-53105, Bonn, Germany [T. P., A. W., A. K., J. K., B. H., N. S., H. K. W.], A. v. D., O. D. W.]; Department of Pathology, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, H3T 1E2 Canada [S. A.]; Departments of Neurosurgery [J. T.] and Pediatric Neurosurgery [N. S.], University of Würzburg, D-97080 Würzburg, Germany; Department of Pediatric Hematology and Oncology, University of Cologne, D-50925 Cologne, Germany [F. B.]; Centre for Molecular and Cellular Biology, University of Queensland, St. Lucia, QLD 4072, Australia [B. W., C. W.]; The Queensland Institute of Medical Research, Royal Brisbane Hospital, Brisbane, QLD 4029, Australia [G. C-T.]

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 continous 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.

¹ This work was supported by Grant SFB400-C2 from the Deutsche Forschungsgemeinschaft and grants from Deutsche Krebshilfe and the Australian National Health and Medical Research Council.

² To whom requests for reprints should be addressed. Phone: 49-228-287-4398/-4332; Fax: 49-228-287-4331; E-mail: pietsch-t@uni-bonn.de.

Received 1/29/97. Accepted 4/20/97.

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