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, Lawrence (Larry) Sherman, Miriam J. Smith, Anat O. Stemmer-Rachamimov, Jeremie Vitte, Marco Giovannini

    Research output: Contribution to journalArticle

    88 Citations (Scopus)

    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

    Fingerprint

    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, Lawrence (Larry); 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, LL, 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, Lawrence (Larry) ; 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.
    @article{fe5e89d8b9354b9d9a84e250401cfe5d,
    title = "Update from the 2011 International Schwannomatosis Workshop: From genetics to diagnostic criteria",
    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.",
    keywords = "Neurofibromatoses, Rhabdoid tumor, Schwannoma",
    author = "Plotkin, {Scott R.} and Blakeley, {Jaishri O.} and Evans, {D. Gareth} and Hanemann, {C. Oliver} and Hulsebos, {Theo J M} and Kim Hunter-Schaedle and Kalpana, {Ganjam V.} and Bruce Korf and Ludwine Messiaen and Laura Papi and Nancy Ratner and Sherman, {Lawrence (Larry)} and Smith, {Miriam J.} and Stemmer-Rachamimov, {Anat O.} and Jeremie Vitte and Marco Giovannini",
    year = "2013",
    month = "3",
    doi = "10.1002/ajmg.a.35760",
    language = "English (US)",
    volume = "161",
    pages = "405--416",
    journal = "American Journal of Medical Genetics, Part A",
    issn = "1552-4825",
    publisher = "Wiley-Liss Inc.",
    number = "3",

    }

    TY - JOUR

    T1 - Update from the 2011 International Schwannomatosis Workshop

    T2 - From genetics to diagnostic criteria

    AU - Plotkin, Scott R.

    AU - Blakeley, Jaishri O.

    AU - Evans, D. Gareth

    AU - Hanemann, C. Oliver

    AU - Hulsebos, Theo J M

    AU - Hunter-Schaedle, Kim

    AU - Kalpana, Ganjam V.

    AU - Korf, Bruce

    AU - Messiaen, Ludwine

    AU - Papi, Laura

    AU - Ratner, Nancy

    AU - Sherman, Lawrence (Larry)

    AU - Smith, Miriam J.

    AU - Stemmer-Rachamimov, Anat O.

    AU - Vitte, Jeremie

    AU - Giovannini, Marco

    PY - 2013/3

    Y1 - 2013/3

    N2 - 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.

    AB - 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.

    KW - Neurofibromatoses

    KW - Rhabdoid tumor

    KW - Schwannoma

    UR - http://www.scopus.com/inward/record.url?scp=84874217623&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84874217623&partnerID=8YFLogxK

    U2 - 10.1002/ajmg.a.35760

    DO - 10.1002/ajmg.a.35760

    M3 - Article

    VL - 161

    SP - 405

    EP - 416

    JO - American Journal of Medical Genetics, Part A

    JF - American Journal of Medical Genetics, Part A

    SN - 1552-4825

    IS - 3

    ER -