ANALYSIS OF MUTATIONS IN THE SCH GENE IN SCHWANNOMAS

Schwannomas are benign tumors of cranial, spinal, and other nerve shea ths that develop sporadically or are inherited as part of neurofibroma tosis type 2 (NF2). The NF2 gene (SCH) on chromosome 22 has recently b een identified and shown to be inactivated by mutation and allele loss in some schwannomas. However, only limited regions in the SCH coding region were examined for mutations. We have extended these studies by screening virtually all coding sequences of the SCH gene (95% coverage ) and adjacent splice site sequences for the presence of mutations in 48 schwannomas. All tumors (34 vestibular schwannomas and 14 schwannom as of other locations) were additionally characterized for allele loss on chromosome 22. By PCR-DGGE screening of the 16 known exons of the SCH gene, 22 mutations were found. Most of these give rise to a premat ure stop codon and are expected to result in the synthesis of a trunca ted gene product (schwannomin). Although there was no apparent hotspot for mutations, 16 of the 22 mutations occurred in the first eight exo ns or adjacent splice site sequences of the SCH gene. In several vesti bular as well as other schwannomas loss of one SCH allele and mutation al inactivation of the second allele were identified in the same tumor . Our data indicate that the SCH gene is implicated in the development of schwannomas of all locations in the nervous system. (C) 1994 Wiley -Liss, Inc.