title: Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas.
abstract: Schwannomatosis is characterized by the onset of multiple intracranial, spinal, or peripheral schwannomas, without involvement of the vestibular nerve, which is instead pathognomonic of neurofibromatosis type 2 (NF2). Recently, a schwannomatosis family with a germline mutation of the SMARCB1 gene on chromosome 22 has been described. We report on the molecular analysis of the SMARCB1 and NF2 genes in a series of 21 patients with schwannomatosis and in eight schwannomatosis-associated tumors from four different patients. A novel germline SMARCB1 mutation was found in one patient; inactivating somatic mutations of NF2, associated with loss of heterozygosity (LOH) of 22q, were found in two schwannomas of this patient. This is the second report of a germline SMARCB1 mutation in patients affected by schwannomatosis and the first report of SMARCB1 mutations associated with somatic NF2 mutations in schwannomatosis-associated tumors. The latter observation suggests that a four-hit mechanism involving the SMARCB1 and NF2 genes may be implicated in schwannomatosis-related tumorigenesis.
authors: Medical Genetics Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
authors: Roberta
authors: R
authors: Sestini
authors: Costanza
authors: C
authors: Bacci
authors: Aldesia
authors: A
authors: Provenzano
authors: Maurizio
authors: M
authors: Genuardi
authors: Laura
authors: L
authors: Papi
mesh_terms: D000328:Adult; D001483:Base Sequence; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009442:Neurilemmoma / Q000235:genetics*; D025581:Neurofibromin 2 / Q000235:genetics*; D010524:Peripheral Nervous System Neoplasms / Q000235:genetics*; D000071796:SMARCB1 Protein; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D025581:Neurofibromin 2; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors