Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma

Over the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline DNMT3A gain-of-function variants in two patients with head and neck paragangliomas causing a...

Descripción completa

Detalles Bibliográficos
Autores: Mellid, Sara, Coloma, Javier, Calsina, Bruna, Monteagudo, María, Roldán Romero, Juan M., Santos, María, Leandro García, Luis J., Lanillos, Javier, Martínez Montes, Ángel M., Rodríguez Antona, Cristina, Montero Conde, Cristina, Martínez López, Joaquín, Ayala, Rosa, Matias-Guiu, Xavier, 1958-, Robledo, Mercedes, Cascón, Alberto
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/173844
Acceso en línea:https://hdl.handle.net/2445/173844
Access Level:acceso abierto
Palabra clave:Tumors
Càncer de tiroide
Thyroid gland cancer
id ES_ee29e777b38f2e53e0ff40739a224799
oai_identifier_str oai:diposit.ub.edu:2445/173844
network_acronym_str ES
network_name_str España
repository_id_str
spelling Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid CarcinomaMellid, SaraColoma, JavierCalsina, BrunaMonteagudo, MaríaRoldán Romero, Juan M.Santos, MaríaLeandro García, Luis J.Lanillos, JavierMartínez Montes, Ángel M.Rodríguez Antona, CristinaMontero Conde, CristinaMartínez López, JoaquínAyala, RosaMatias-Guiu, Xavier, 1958-Robledo, MercedesCascón, AlbertoTumorsCàncer de tiroideTumorsThyroid gland cancerOver the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline DNMT3A gain-of-function variants in two patients with head and neck paragangliomas causing a characteristic hypermethylated DNA profile. Here, whole-exome sequencing identifies a novel germline DNMT3A variant (p.Gly332Arg) in a patient with bilateral carotid paragangliomas, papillary thyroid carcinoma and idiopathic intellectual disability. The variant, located in the Pro-Trp-Trp-Pro (PWWP) domain of the protein involved in chromatin targeting, affects a residue mutated in papillary thyroid tumors and located between the two residues found mutated in microcephalic dwarfism patients. Structural modelling of the variant in the DNMT3A PWWP domain predicts that the interaction with H3K36me3 will be altered. An increased methylation of DNMT3A target genes, compatible with a gain-of-function effect of the alteration, was observed in saliva DNA from the proband and in one independent acute myeloid leukemia sample carrying the same p.Gly332Arg variant. Although further studies are needed to support a causal role of DNMT3A variants in paraganglioma, the description of a new DNMT3A alteration in a patient with multiple clinical features suggests a heterogeneous phenotypic spectrum related to DNMT3A germline variants.MDPI2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/173844Articles 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/10.3390/cancers12113304Cancers, 2020, vol. 12, num.11https://doi.org/10.3390/cancers12113304cc by (c) Mellid et al., 2020http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1738442026-05-27T06:46:51Z
dc.title.none.fl_str_mv Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
title Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
spellingShingle Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
Mellid, Sara
Tumors
Càncer de tiroide
Tumors
Thyroid gland cancer
title_short Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
title_full Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
title_fullStr Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
title_full_unstemmed Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
title_sort Novel DNMT3A Germline Variant in a Patient with Multiple Paragangliomas and Papillary Thyroid Carcinoma
dc.creator.none.fl_str_mv Mellid, Sara
Coloma, Javier
Calsina, Bruna
Monteagudo, María
Roldán Romero, Juan M.
Santos, María
Leandro García, Luis J.
Lanillos, Javier
Martínez Montes, Ángel M.
Rodríguez Antona, Cristina
Montero Conde, Cristina
Martínez López, Joaquín
Ayala, Rosa
Matias-Guiu, Xavier, 1958-
Robledo, Mercedes
Cascón, Alberto
author Mellid, Sara
author_facet Mellid, Sara
Coloma, Javier
Calsina, Bruna
Monteagudo, María
Roldán Romero, Juan M.
Santos, María
Leandro García, Luis J.
Lanillos, Javier
Martínez Montes, Ángel M.
Rodríguez Antona, Cristina
Montero Conde, Cristina
Martínez López, Joaquín
Ayala, Rosa
Matias-Guiu, Xavier, 1958-
Robledo, Mercedes
Cascón, Alberto
author_role author
author2 Coloma, Javier
Calsina, Bruna
Monteagudo, María
Roldán Romero, Juan M.
Santos, María
Leandro García, Luis J.
Lanillos, Javier
Martínez Montes, Ángel M.
Rodríguez Antona, Cristina
Montero Conde, Cristina
Martínez López, Joaquín
Ayala, Rosa
Matias-Guiu, Xavier, 1958-
Robledo, Mercedes
Cascón, Alberto
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Tumors
Càncer de tiroide
Tumors
Thyroid gland cancer
topic Tumors
Càncer de tiroide
Tumors
Thyroid gland cancer
description Over the past few years, next generation technologies have been applied to unravel the genetics of rare inherited diseases, facilitating the discovery of new susceptibility genes. We recently found germline DNMT3A gain-of-function variants in two patients with head and neck paragangliomas causing a characteristic hypermethylated DNA profile. Here, whole-exome sequencing identifies a novel germline DNMT3A variant (p.Gly332Arg) in a patient with bilateral carotid paragangliomas, papillary thyroid carcinoma and idiopathic intellectual disability. The variant, located in the Pro-Trp-Trp-Pro (PWWP) domain of the protein involved in chromatin targeting, affects a residue mutated in papillary thyroid tumors and located between the two residues found mutated in microcephalic dwarfism patients. Structural modelling of the variant in the DNMT3A PWWP domain predicts that the interaction with H3K36me3 will be altered. An increased methylation of DNMT3A target genes, compatible with a gain-of-function effect of the alteration, was observed in saliva DNA from the proband and in one independent acute myeloid leukemia sample carrying the same p.Gly332Arg variant. Although further studies are needed to support a causal role of DNMT3A variants in paraganglioma, the description of a new DNMT3A alteration in a patient with multiple clinical features suggests a heterogeneous phenotypic spectrum related to DNMT3A germline variants.
publishDate 2020
dc.date.none.fl_str_mv 2020
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/2445/173844
url https://hdl.handle.net/2445/173844
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/10.3390/cancers12113304
Cancers, 2020, vol. 12, num.11
https://doi.org/10.3390/cancers12113304
dc.rights.none.fl_str_mv cc by (c) Mellid et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Mellid et al., 2020
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 MDPI
publisher.none.fl_str_mv MDPI
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
_version_ 1869423620094164992
score 15.198674

Similares en LA Referencia