Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb

Background: A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a som...

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Autores: Castellanos, Elisabeth, Bielsa Marsol, Isabel, Carrato, Cristina, Rosas, Inma, Solanes, Ares, Hostalot, Cristina, Amilibia, Emilio, Prades, José, Roca Ribas, Francesc, Lázaro García, Conxi, Blanco Guillermo, Ignacio, Serra Arenas, Eduard, NF2 Multidisciplinary Clinics HUGTiP-ICO-IMPPC
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/126155
Acceso en línea:https://hdl.handle.net/2445/126155
Access Level:acceso abierto
Palabra clave:Neurofibromatosi
Genètica mèdica
Neurofibromatosis
Medical genetics
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spelling Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limbCastellanos, ElisabethBielsa Marsol, IsabelCarrato, CristinaRosas, InmaSolanes, AresHostalot, CristinaAmilibia, EmilioPrades, JoséRoca Ribas, FrancescLázaro García, ConxiBlanco Guillermo, IgnacioSerra Arenas, EduardNF2 Multidisciplinary Clinics HUGTiP-ICO-IMPPCNeurofibromatosiGenètica mèdicaNeurofibromatosisMedical geneticsBackground: A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivation of the NF2 gene. However, SMARCB1-associated schwannomas follow a four-hit, three-step model, in which both alleles of SMARCB1 and NF2 genes are inactivated in the tumor, with one of the steps being always the loss of a big part of chromosome 22 involving both loci. Case presentation: Here we report a 36-year-old woman who only presented multiple subcutaneous schwannomas on her right leg. To help discriminate between both possible diagnoses, an exhaustive molecular genetic and genomic analysis was performed on two schwannomas of the patient, consisting in cDNA and DNA sequencing, MLPA, microsatellite multiplex PCR and SNP-array analyses. The loss of a big part of chromosome 22 (22q12.1q13.33) was identified in both tumors. However, this loss involved the NF2 but not the SMARCB1 locus. SNP-array analysis revealed the presence of the same deletion breakpoint in both schwannomas, indicating that this alteration was actually the first NF2 inactivating hit. In addition, a distinct NF2 point mutation in each tumor was identified, representing independent second hits. In accordance with these results, no deletions or point mutations in the SMARCB1 gene were identified. None of the mutations were present in the blood. Two of the patient's children inherited chromosome 22 deleted in schwannomas of the mother, but in its wild type form. Conclusions: These results conclusively confirm the segmental mosaic NF2 nature of the clinical phenotype presented.BioMed Central Ltd2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/126155Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1186/s12920-015-0076-2BMC Medical Genomics, 2015, vol. 8, num. 2https://doi.org/10.1186/s12920-015-0076-2cc by (c) Castellanos et al., 2015http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1261552026-05-27T06:46:51Z
dc.title.none.fl_str_mv Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb
title Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb
spellingShingle Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb
Castellanos, Elisabeth
Neurofibromatosi
Genètica mèdica
Neurofibromatosis
Medical genetics
title_short Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb
title_full Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb
title_fullStr Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb
title_full_unstemmed Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb
title_sort Segmental neurofibromatosis type 2: discriminating two hit from four hit in a patient presenting multiple schwannomas confined to one limb
dc.creator.none.fl_str_mv Castellanos, Elisabeth
Bielsa Marsol, Isabel
Carrato, Cristina
Rosas, Inma
Solanes, Ares
Hostalot, Cristina
Amilibia, Emilio
Prades, José
Roca Ribas, Francesc
Lázaro García, Conxi
Blanco Guillermo, Ignacio
Serra Arenas, Eduard
NF2 Multidisciplinary Clinics HUGTiP-ICO-IMPPC
author Castellanos, Elisabeth
author_facet Castellanos, Elisabeth
Bielsa Marsol, Isabel
Carrato, Cristina
Rosas, Inma
Solanes, Ares
Hostalot, Cristina
Amilibia, Emilio
Prades, José
Roca Ribas, Francesc
Lázaro García, Conxi
Blanco Guillermo, Ignacio
Serra Arenas, Eduard
NF2 Multidisciplinary Clinics HUGTiP-ICO-IMPPC
author_role author
author2 Bielsa Marsol, Isabel
Carrato, Cristina
Rosas, Inma
Solanes, Ares
Hostalot, Cristina
Amilibia, Emilio
Prades, José
Roca Ribas, Francesc
Lázaro García, Conxi
Blanco Guillermo, Ignacio
Serra Arenas, Eduard
NF2 Multidisciplinary Clinics HUGTiP-ICO-IMPPC
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Neurofibromatosi
Genètica mèdica
Neurofibromatosis
Medical genetics
topic Neurofibromatosi
Genètica mèdica
Neurofibromatosis
Medical genetics
description Background: A clinical overlap exists between mosaic Neurofibromatosis Type 2 and sporadic Schwannomatosis conditions. In these cases a molecular analysis of tumors is recommended for a proper genetic diagnostics. This analysis is challenged by the fact that schwannomas in both conditions bear a somatic double inactivation of the NF2 gene. However, SMARCB1-associated schwannomas follow a four-hit, three-step model, in which both alleles of SMARCB1 and NF2 genes are inactivated in the tumor, with one of the steps being always the loss of a big part of chromosome 22 involving both loci. Case presentation: Here we report a 36-year-old woman who only presented multiple subcutaneous schwannomas on her right leg. To help discriminate between both possible diagnoses, an exhaustive molecular genetic and genomic analysis was performed on two schwannomas of the patient, consisting in cDNA and DNA sequencing, MLPA, microsatellite multiplex PCR and SNP-array analyses. The loss of a big part of chromosome 22 (22q12.1q13.33) was identified in both tumors. However, this loss involved the NF2 but not the SMARCB1 locus. SNP-array analysis revealed the presence of the same deletion breakpoint in both schwannomas, indicating that this alteration was actually the first NF2 inactivating hit. In addition, a distinct NF2 point mutation in each tumor was identified, representing independent second hits. In accordance with these results, no deletions or point mutations in the SMARCB1 gene were identified. None of the mutations were present in the blood. Two of the patient's children inherited chromosome 22 deleted in schwannomas of the mother, but in its wild type form. Conclusions: These results conclusively confirm the segmental mosaic NF2 nature of the clinical phenotype presented.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/126155
url https://hdl.handle.net/2445/126155
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1186/s12920-015-0076-2
BMC Medical Genomics, 2015, vol. 8, num. 2
https://doi.org/10.1186/s12920-015-0076-2
dc.rights.none.fl_str_mv cc by (c) Castellanos et al., 2015
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Castellanos et al., 2015
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BioMed Central Ltd
publisher.none.fl_str_mv BioMed Central Ltd
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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