Evidence of a four-hit mechanism involving SMARCB1 and NF2 in schwannomatosis-associated schwannomas

✍ Scribed by Roberta Sestini; Costanza Bacci; Aldesia Provenzano; Maurizio Genuardi; Laura Papi

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 236 KB
• Volume: 29
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.20679

✦ Synopsis

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.