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...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Publication date: | 2020 |
| Country: | España |
| Institution: | Instituto de Salud Carlos III (ISCIII) |
| Repository: | Repisalud |
| Language: | English |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/11420 |
| Online Access: | http://hdl.handle.net/20.500.12105/11420 |
| Access Level: | Open access |
| Keyword: | Mosaicism Cohort Studies Genetic Counseling Genotype High-Throughput Nucleotide Sequencing Humans Mutation Phenotype Retinoblastoma |
| _version_ | 1878731554510864384 |
|---|---|
| author | Rodriguez-Martin, Carlos |
| 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 |
| author_browse | Abelairas, Jose Alonso, Javier Cuesta de la Plaza, Isabel Fernández-Teijeiro, Ana Ferreres, Joan Carles Gomez-Mariano, Gema Maria González-Campora, Ricardo Martinez-Delgado, Beatriz Martín-Begué, Nieves Monzon-Fernandez, Sara Posada De la Paz, Manuel Rios-Moreno, María José Robledo, Cristina Rodriguez-Martin, Carlos Sabado, Constantino Sastre, Ana Zaballos, Ángel |
| 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 |
| collection | Repisalud |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_31fd3901ef5ff6de922b0f3bc52e2b67 |
| institution | Instituto de Salud Carlos III (ISCIII) |
| instname_str | Instituto de Salud Carlos III (ISCIII) |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:repisalud.isciii.es:20.500.12105/11420 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | Springer |
| publisherStr | Springer |
| reponame_str | Repisalud |
| spelling | Frequency of low-level and high-level mosaicism in sporadic retinoblastoma: genotype-phenotype relationships. 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 Mosaicism Cohort Studies Genetic Counseling Genotype High-Throughput Nucleotide Sequencing Humans Mutation Phenotype Retinoblastoma 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. Springer http://hdl.handle.net/20.500.12105/11420 |
| 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 | 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_short | 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. |
| topic | Mosaicism Cohort Studies Genetic Counseling Genotype High-Throughput Nucleotide Sequencing Humans Mutation Phenotype Retinoblastoma |
| topic_facet | Mosaicism Cohort Studies Genetic Counseling Genotype High-Throughput Nucleotide Sequencing Humans Mutation Phenotype Retinoblastoma |
| url | http://hdl.handle.net/20.500.12105/11420 |