Evidence of a Four-Hit Mechanism... : Human Mutation (original) (raw)

Evidence of a Four-Hit Mechanism Involving SMARCB1 and NF2 in Schwannomatosis-Associated Schwannomas

Roberta Sestini
Costanza Bacci
Aldesia Provenzano
Maurizio Genuardi
Laura Papi

Human Mutation

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227

231

February 2008

| DOI: 10.1002/humu.20679

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. Hum Mutat 29(2), 227–231, 2008. © 2007 Wiley-Liss, Inc.