title: INI1 mutations in meningiomas at a potential hotspot in exon 9.
abstract: Rhabdoid tumours have been shown to carry somatic mutations in the INI1 (SMARCB1/hSNF5) gene. A considerable fraction of these tumours exhibit allelic losses on chromosome 22. Allelic loss on 22q also is characteristic for meningiomas, however most of these alterations are considered to be associated with mutations of the NF2 gene. We examined a series of 126 meningiomas for 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 INI1. Our observations were reproduced both by using DNA from a new round of extraction and by employing overlapping primers. This mutational hotspot therefore 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 chromosome 22 that may be important for the genesis of meningiomas.
authors.affiliation: Department of Neuropathology, Charité, Humboldt University, Berlin, 13353, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Schmitz
authors.forename: W
authors.initials: W
authors.lastname: Mueller
authors.forename: M
authors.initials: M
authors.lastname: Weber
authors.forename: N
authors.initials: N
authors.lastname: Sévenet
authors.forename: O
authors.initials: O
authors.lastname: Delattre
authors.forename: A
authors.initials: A
authors.lastname: von Deimling
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D019656:Loss of Heterozygosity; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D000071796:SMARCB1 Protein; D014157:Transcription Factors
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors