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Sporadic Medulloblastomas Contain PTCH Mutations¹

Departments of Neurosurgery [C. R.], Laboratory Medicine and Pathology [R. B. J., L. F., D. H., B. A., C. D. J.], Mayo Clinic and Foundation, Rochester, Minnesota 55905, and University of Utah Health Sciences Center, Salt Lake City, Utah 84132 [D. W. F.]

Nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin's syndrome, is an autosomal dominant disorder that predisposes to developmental defects and various forms of cancer. PTCH was recently proposed as a candidate gene for NBCCS due to its frequent mutation in basal cell carcinomas, the cancer most often associated with this syndrome. Another NBCCS-associated cancer is medulloblastoma, a common central nervous system tumor in children. Most medulloblastomas, however, occur without indication of an inherited predisposition. We have examined 24 sporadic medulloblastomas for loss of heterozygosity (LOH) at loci flanking as well as within PTCH. In cases with LOH, single-strand conformational polymorphism and sequencing analysis were performed to determine the status of the remaining PTCH allele. Microsatellite analysis indicated LOH of PTCH in 5 of 24 tumors, and in three of these cases a mutation of the remaining allele was identified. Two of the mutations were duplication insertions, and the third consisted of a single base deletion. It is interesting that all three mutations occur in exon 17 of the PTCH gene. These data suggest that inactivation of PTCH function is involved in the development of at least a subset of sporadic medulloblastomas.

¹ This work was supported by National Cancer Institute Grants CA55728 and CA50905.

² To whom requests for reprints should be addressed, at Department of Neurosurgery, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905. Phone: (507) 284-3514; Fax: (507) 284-5206; E-mail: raffel.corey@mayo.edu.

Received 12/ 5/96. Accepted 1/17/97.

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