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The Molecular Genetics of Schwannomatosis

  1. Theo JM Hulsebos

Published Online: 15 MAR 2009

DOI: 10.1002/9780470015902.a0021427

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How to Cite

Hulsebos, T. J. 2009. The Molecular Genetics of Schwannomatosis. eLS. .

Author Information

  1. Academic Medical Center, Neurogenetics Laboratory, Amsterdam, The Netherlands

Publication History

  1. Published Online: 15 MAR 2009

Abstract

Schwannomatosis is characterized by the development of multiple schwannomas, but without the involvement of vestibular schwannomas. Presence of the latter is the hallmark of neurofibromatosis type 2 (NF2). Recent studies in families with schwannomatosis have excluded the NF2 gene on chromosome 22 as the germline-transmissible schwannomatosis gene. However, this gene was found to be somatically inactivated in schwannomas of the patients. In 2007, the INI1/SMARCB1 gene on chromosome 22 was identified as a strong candidate for the schwannomatosis-predisposing gene. Subsequent studies have confirmed the involvement of this tumour suppressor gene in 40–50% of familial and about 10% of sporadic cases. INI1/SMARCB1 had earlier been found to be implicated in the development of malignant rhabdoid tumours, which are aggressive tumours of early childhood. It remains to be explained how INI1/SMARCB1 can be involved in the development of benign schwannomas and of malignant rhabdoid tumours as well.

Key concepts

  • Schwannomatosis is characterized by the development of multiple schwannomas but no vestibular schwannomas, which are diagnostic of neurofibromatosis type 2 (NF2).

  • INI1/SMARCB1 on chromosome 22 is a schwannomatosis-predisposing gene. Constitutional mutations in this gene are found in 40–50% of familial cases and about 10% of sporadic cases.

  • INI1/SMARCB1 is a tumour suppressor gene of which the second wild-type copy is found to be inactivated in the schwannomas of these patients.

  • Inactivating mutations in the NF2 gene are also found in the schwannomas of schwannomatosis patients, but these are only somatically acquired.

  • The INI1/SMARCB1 protein is a core subunit of the SWI/SNF complex. The SWI/SNF complex is involved in chromatin-remodelling and in cancer development.

  • INI1/SMARCB1 is also implicated in the development of malignant rhabdoid tumours, which are aggressive tumours of early childhood. Patients with rhabdoid tumour predisposition syndrome (RTPS) carry a constitutionally mutated INI1/SMARCB1 gene and may develop more than one rhabdoid tumour.

  • It remains to be clarified how INI1/SMARCB1 can be involved in the development of two tumour types, schwannomas and rhabdoid tumours, with very different histologies and malignancy grades.

Keywords:

  • schwannomatosis;
  • schwannoma;
  • rhabdoid tumour;
  • INI1/SMARCB1;
  • NF2