Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria

Scott R. Plotkin, Jaishri O. Blakeley, D. Gareth Evans, C. Oliver Hanemann, Theo J M Hulsebos, Kim Hunter-Schaedle, Ganjam V. Kalpana, Bruce Korf, Ludwine Messiaen, Laura Papi, Nancy Ratner, Larry S. Sherman, Miriam J. Smith, Anat O. Stemmer-Rachamimov, Jeremie Vitte, Marco Giovannini

Research output: Contribution to journalArticle

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Abstract

Schwannomatosis is the third major form of neurofibromatosis and is characterized by the development of multiple schwannomas in the absence of bilateral vestibular schwannomas. The 2011 Schwannomatosis Update was organized by the Children's Tumor Foundation (www.ctf.org) and held in Los Angeles, CA, from June 5-8, 2011. This article summarizes the highlights presented at the Conference and represents the "state-of-the-field" in 2011. Genetic studies indicate that constitutional mutations in the SMARCB1 tumor suppressor gene occur in 40-50% of familial cases and in 8-10% of sporadic cases of schwannomatosis. Tumorigenesis is thought to occur through a four-hit, three-step model, beginning with a germline mutation in SMARCB1 (hit 1), followed by loss of a portion of chromosome 22 that contains the second SMARCB1 allele and one NF2 allele (hits 2 and 3), followed by mutation of the remaining wild-type NF2 allele (hit 4). Insights from research on HIV and pediatric rhabdoid tumors have shed light on potential molecular pathways that are dysregulated in schwannomatosis-related schwannomas. Mouse models of schwannomatosis have been developed and promise to further expand our understanding of tumorigenesis and the tumor microenvironment. Clinical reports have described the occurrence of intracranial meningiomas in schwannomatosis patients and in families with germline SMARCB1 mutations. The authors propose updated diagnostic criteria to incorporate new clinical and genetic findings since 2005. In the next 5 years, the authors expect that advances in basic research in the pathogenesis of schwannomatosis will lead toward clinical investigations of potential drug therapies.

Original languageEnglish (US)
Pages (from-to)405-416
Number of pages12
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number3
DOIs
StatePublished - Mar 2013

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Education
Germ-Line Mutation
Alleles
Neurilemmoma
Carcinogenesis
Rhabdoid Tumor
Chromosomes, Human, Pair 22
Mutation
Neurofibromatoses
Tumor Microenvironment
Acoustic Neuroma
Los Angeles
Meningioma
Schwannomatosis
Tumor Suppressor Genes
Research
HIV
Pediatrics
Drug Therapy
Neoplasms

Keywords

  • Neurofibromatoses
  • Rhabdoid tumor
  • Schwannoma

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Plotkin, S. R., Blakeley, J. O., Evans, D. G., Hanemann, C. O., Hulsebos, T. J. M., Hunter-Schaedle, K., ... Giovannini, M. (2013). Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria. American Journal of Medical Genetics, Part A, 161(3), 405-416. https://doi.org/10.1002/ajmg.a.35760

Update from the 2011 International Schwannomatosis Workshop : From genetics to diagnostic criteria. / Plotkin, Scott R.; Blakeley, Jaishri O.; Evans, D. Gareth; Hanemann, C. Oliver; Hulsebos, Theo J M; Hunter-Schaedle, Kim; Kalpana, Ganjam V.; Korf, Bruce; Messiaen, Ludwine; Papi, Laura; Ratner, Nancy; Sherman, Larry S.; Smith, Miriam J.; Stemmer-Rachamimov, Anat O.; Vitte, Jeremie; Giovannini, Marco.

In: American Journal of Medical Genetics, Part A, Vol. 161, No. 3, 03.2013, p. 405-416.

Research output: Contribution to journalArticle

Plotkin, SR, Blakeley, JO, Evans, DG, Hanemann, CO, Hulsebos, TJM, Hunter-Schaedle, K, Kalpana, GV, Korf, B, Messiaen, L, Papi, L, Ratner, N, Sherman, LS, Smith, MJ, Stemmer-Rachamimov, AO, Vitte, J & Giovannini, M 2013, 'Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria', American Journal of Medical Genetics, Part A, vol. 161, no. 3, pp. 405-416. https://doi.org/10.1002/ajmg.a.35760
Plotkin, Scott R. ; Blakeley, Jaishri O. ; Evans, D. Gareth ; Hanemann, C. Oliver ; Hulsebos, Theo J M ; Hunter-Schaedle, Kim ; Kalpana, Ganjam V. ; Korf, Bruce ; Messiaen, Ludwine ; Papi, Laura ; Ratner, Nancy ; Sherman, Larry S. ; Smith, Miriam J. ; Stemmer-Rachamimov, Anat O. ; Vitte, Jeremie ; Giovannini, Marco. / Update from the 2011 International Schwannomatosis Workshop : From genetics to diagnostic criteria. In: American Journal of Medical Genetics, Part A. 2013 ; Vol. 161, No. 3. pp. 405-416.
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