Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.

Somatic mutational mosaicism is a common feature of monogenic genetic disorders, particularly in diseases such as retinoblastoma, with high rates of de novo mutations. The detection and quantification of mosaicism is particularly relevant in these diseases, since it has important implications for ge...

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Autores: Rodriguez-Martin, Carlos, Robledo, Cristina, Gomez-Mariano, Gema Maria, Monzon-Fernandez, Sara, Sastre, Ana, Abelairas, Jose, Sabado, Constantino, Martín-Begué, Nieves, Ferreres, Joan Carles, Fernández-Teijeiro, Ana, González-Campora, Ricardo, Rios-Moreno, María José, Zaballos, Ángel, Cuesta de la Plaza, Isabel, Martinez-Delgado, Beatriz, Posada De la Paz, Manuel, Alonso, Javier
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/11420
Acceso en línea:http://hdl.handle.net/20.500.12105/11420
Access Level:acceso abierto
Palabra clave:Mosaicism
Cohort Studies
Genetic Counseling
Genotype
High-Throughput Nucleotide Sequencing
Humans
Mutation
Phenotype
Retinoblastoma
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spelling Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.Rodriguez-Martin, CarlosRobledo, CristinaGomez-Mariano, Gema MariaMonzon-Fernandez, SaraSastre, AnaAbelairas, JoseSabado, ConstantinoMartín-Begué, NievesFerreres, Joan CarlesFernández-Teijeiro, AnaGonzález-Campora, RicardoRios-Moreno, María JoséZaballos, ÁngelCuesta de la Plaza, IsabelMartinez-Delgado, BeatrizPosada De la Paz, ManuelAlonso, JavierMosaicismCohort StudiesGenetic CounselingGenotypeHigh-Throughput Nucleotide SequencingHumansMutationPhenotypeRetinoblastomaSomatic mutational mosaicism is a common feature of monogenic genetic disorders, particularly in diseases such as retinoblastoma, with high rates of de novo mutations. The detection and quantification of mosaicism is particularly relevant in these diseases, since it has important implications for genetic counseling, patient management, and probably also on disease onset and progression. In order to assess the rate of somatic mosaicism (high- and low-level mosaicism) in sporadic retinoblastoma patients, we analyzed a cohort of 153 patients with sporadic retinoblastoma using ultra deep next-generation sequencing. High-level mosaicism was detected in 14 out of 100 (14%) bilateral patients and in 11 out of 29 (38%) unilateral patients in whom conventional Sanger sequencing identified a pathogenic mutation in blood DNA. In addition, low-level mosaicism was detected in 3 out of 16 (19%) unilateral patients in whom conventional screening was negative in blood DNA. Our results also reveal that mosaicism was associated to delayed retinoblastoma onset particularly in unilateral patients. Finally we compared the level of mosaicism in different tissues to identify the best DNA source to identify mosaicism in retinoblastoma patients. In light of these results we recommended analyzing the mosaic status in all retinoblastoma patients using accurate techniques such as next-generation sequencing, even in those cases in which conventional Sanger sequencing identified a pathogenic mutation in blood DNA. Our results suggest that a significant proportion of those cases are truly mosaics that could have been overlooked. This information should be taking into consideration in the management and genetic counseling of retinoblastoma patients and families.SpringerInstituto de Salud Carlos IIIAsociación Pablo Ugarte contra el cáncer infantilFundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de EwingMinisterio de Economía y Competitividad (España)Centro de Investigación Biomedica en Red - CIBERAsociación Todos somos Iván20202020-11-2520202020-01-0120202020-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/11420reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/114202026-06-12T12:43:37Z
dc.title.none.fl_str_mv Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.
title Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.
spellingShingle Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.
Rodriguez-Martin, Carlos
Mosaicism
Cohort Studies
Genetic Counseling
Genotype
High-Throughput Nucleotide Sequencing
Humans
Mutation
Phenotype
Retinoblastoma
title_short Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.
title_full Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.
title_fullStr Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.
title_full_unstemmed Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.
title_sort Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships.
dc.creator.none.fl_str_mv Rodriguez-Martin, Carlos
Robledo, Cristina
Gomez-Mariano, Gema Maria
Monzon-Fernandez, Sara
Sastre, Ana
Abelairas, Jose
Sabado, Constantino
Martín-Begué, Nieves
Ferreres, Joan Carles
Fernández-Teijeiro, Ana
González-Campora, Ricardo
Rios-Moreno, María José
Zaballos, Ángel
Cuesta de la Plaza, Isabel
Martinez-Delgado, Beatriz
Posada De la Paz, Manuel
Alonso, Javier
author Rodriguez-Martin, Carlos
author_facet Rodriguez-Martin, Carlos
Robledo, Cristina
Gomez-Mariano, Gema Maria
Monzon-Fernandez, Sara
Sastre, Ana
Abelairas, Jose
Sabado, Constantino
Martín-Begué, Nieves
Ferreres, Joan Carles
Fernández-Teijeiro, Ana
González-Campora, Ricardo
Rios-Moreno, María José
Zaballos, Ángel
Cuesta de la Plaza, Isabel
Martinez-Delgado, Beatriz
Posada De la Paz, Manuel
Alonso, Javier
author_role author
author2 Robledo, Cristina
Gomez-Mariano, Gema Maria
Monzon-Fernandez, Sara
Sastre, Ana
Abelairas, Jose
Sabado, Constantino
Martín-Begué, Nieves
Ferreres, Joan Carles
Fernández-Teijeiro, Ana
González-Campora, Ricardo
Rios-Moreno, María José
Zaballos, Ángel
Cuesta de la Plaza, Isabel
Martinez-Delgado, Beatriz
Posada De la Paz, Manuel
Alonso, Javier
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Asociación Pablo Ugarte contra el cáncer infantil
Fundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing
Ministerio de Economía y Competitividad (España)
Centro de Investigación Biomedica en Red - CIBER
Asociación Todos somos Iván
dc.subject.none.fl_str_mv Mosaicism
Cohort Studies
Genetic Counseling
Genotype
High-Throughput Nucleotide Sequencing
Humans
Mutation
Phenotype
Retinoblastoma
topic Mosaicism
Cohort Studies
Genetic Counseling
Genotype
High-Throughput Nucleotide Sequencing
Humans
Mutation
Phenotype
Retinoblastoma
description Somatic mutational mosaicism is a common feature of monogenic genetic disorders, particularly in diseases such as retinoblastoma, with high rates of de novo mutations. The detection and quantification of mosaicism is particularly relevant in these diseases, since it has important implications for genetic counseling, patient management, and probably also on disease onset and progression. In order to assess the rate of somatic mosaicism (high- and low-level mosaicism) in sporadic retinoblastoma patients, we analyzed a cohort of 153 patients with sporadic retinoblastoma using ultra deep next-generation sequencing. High-level mosaicism was detected in 14 out of 100 (14%) bilateral patients and in 11 out of 29 (38%) unilateral patients in whom conventional Sanger sequencing identified a pathogenic mutation in blood DNA. In addition, low-level mosaicism was detected in 3 out of 16 (19%) unilateral patients in whom conventional screening was negative in blood DNA. Our results also reveal that mosaicism was associated to delayed retinoblastoma onset particularly in unilateral patients. Finally we compared the level of mosaicism in different tissues to identify the best DNA source to identify mosaicism in retinoblastoma patients. In light of these results we recommended analyzing the mosaic status in all retinoblastoma patients using accurate techniques such as next-generation sequencing, even in those cases in which conventional Sanger sequencing identified a pathogenic mutation in blood DNA. Our results suggest that a significant proportion of those cases are truly mosaics that could have been overlooked. This information should be taking into consideration in the management and genetic counseling of retinoblastoma patients and families.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-11-25
2020
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/11420
url http://hdl.handle.net/20.500.12105/11420
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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