INI1 mutations in meningiomas at a potential hotspot in exon 9

Rhabdoid tumours have been shown to carry somatic mutations in the INI1 (SM ARCB1/hSNF5) gene. A considerable fraction of these tumours exhibit allelic losses on chromosome 22. Allelic loss on 22q also is characteristic for me ningiomas, however most of these alterations are considered to be associate d with mutations of the NF2 gene. We examined a series of 126 meningiomas f or alterations in the INI1 gene. Four identical somatic mutations in exon 9 were detected resulting in an exchange of Arg to His in position 377 of IN I1. Our observations were reproduced both by using DNA from a new round of extraction and by employing overlapping primers. This mutational hotspot th erefore appears to be an important target in the formation of a fraction of meningiomas. In addition, 4 novel polymorphisms of INI1 were characterized . Our data indicate that the INI1 is a second tumour suppressor gene on chr omosome 22 that may be important for the genesis of meningiomas. (C) 2001 C ancer Research Campaign.