Keratinocytic epidermal nevi are associated with mosaic RAS mutations

Background Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A...

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Autores: Hafner, C, Toll, A, Gantner, S, Mauerer, A, Lurkin, I, Acquadro, F, Fernandez-Casado, A, Zwarthoff, EC, Dietmaier, W, Baselga, E, Parera, E, Vicente, A, Casanova, A, Cigudosa, J, Mentzel, T, Pujol, RM, Landthaler, M, Real, FX
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p11443
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11443
https://epub.uni-regensburg.de/36142
Access Level:acceso abierto
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spelling Keratinocytic epidermal nevi are associated with mosaic RAS mutationsHafner, CToll, AGantner, SMauerer, ALurkin, IAcquadro, FFernandez-Casado, AZwarthoff, ECDietmaier, WBaselga, EParera, EVicente, ACasanova, ACigudosa, JMentzel, TPujol, RMLandthaler, MReal, FXBackground Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations. Methods This study screened 72 KEN for activating mutations in RAS genes and other oncogenes. Results Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation. Conclusion These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.BMJ PUBLISHING GROUP2012info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11443https://epub.uni-regensburg.de/36142JOURNAL OF MEDICAL GENETICSISSN: 00222593ISSNe: 14686244reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p114432026-06-14T12:41:47Z
dc.title.none.fl_str_mv Keratinocytic epidermal nevi are associated with mosaic RAS mutations
title Keratinocytic epidermal nevi are associated with mosaic RAS mutations
spellingShingle Keratinocytic epidermal nevi are associated with mosaic RAS mutations
Hafner, C
title_short Keratinocytic epidermal nevi are associated with mosaic RAS mutations
title_full Keratinocytic epidermal nevi are associated with mosaic RAS mutations
title_fullStr Keratinocytic epidermal nevi are associated with mosaic RAS mutations
title_full_unstemmed Keratinocytic epidermal nevi are associated with mosaic RAS mutations
title_sort Keratinocytic epidermal nevi are associated with mosaic RAS mutations
dc.creator.none.fl_str_mv Hafner, C
Toll, A
Gantner, S
Mauerer, A
Lurkin, I
Acquadro, F
Fernandez-Casado, A
Zwarthoff, EC
Dietmaier, W
Baselga, E
Parera, E
Vicente, A
Casanova, A
Cigudosa, J
Mentzel, T
Pujol, RM
Landthaler, M
Real, FX
author Hafner, C
author_facet Hafner, C
Toll, A
Gantner, S
Mauerer, A
Lurkin, I
Acquadro, F
Fernandez-Casado, A
Zwarthoff, EC
Dietmaier, W
Baselga, E
Parera, E
Vicente, A
Casanova, A
Cigudosa, J
Mentzel, T
Pujol, RM
Landthaler, M
Real, FX
author_role author
author2 Toll, A
Gantner, S
Mauerer, A
Lurkin, I
Acquadro, F
Fernandez-Casado, A
Zwarthoff, EC
Dietmaier, W
Baselga, E
Parera, E
Vicente, A
Casanova, A
Cigudosa, J
Mentzel, T
Pujol, RM
Landthaler, M
Real, FX
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
description Background Activating RAS mutations in the germline cause rare developmental disorders such as Costello syndrome. Somatic RAS mutations are found in approximately 30% of human cancers. Keratinocytic epidermal nevi (KEN) represent benign congenital skin lesions arranged along Blaschko's lines. A subgroup of KEN is caused by hotspot oncogenic FGFR3 and PIK3CA mutations in mosaicism, but the majority lack these mutations. Methods This study screened 72 KEN for activating mutations in RAS genes and other oncogenes. Results Activating RAS mutations were identified in 28/72 (39%) of KEN. HRAS was the most commonly affected oncogene (86%), with the HRAS p.G13R substitution representing a new hotspot mutation. Conclusion These results indicate that activating RAS somatic mutations leading to mosaicism result in benign KEN of the skin. Given the prevalence of KEN, mosaic HRAS mutations appear to be more common in patients than germline ones. These findings identify KEN as a mosaic RASopathy and lend further support to the notion that genetic mosaicism is an important contributor to disease.
publishDate 2012
dc.date.none.fl_str_mv 2012
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://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11443
https://epub.uni-regensburg.de/36142
url https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=11443
https://epub.uni-regensburg.de/36142
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BMJ PUBLISHING GROUP
publisher.none.fl_str_mv BMJ PUBLISHING GROUP
dc.source.none.fl_str_mv JOURNAL OF MEDICAL GENETICS
ISSN: 00222593
ISSNe: 14686244
reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
instname_str Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
reponame_str r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
collection r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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