The modular network structure of the mutational landscape of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to thi...

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Autores: Ibáñez, Mariam, Carbonell Caballero, José, Such, Esperanza, García Alonso, Luz, Liquori, Alessandro, López Pavía, María, Llop, Marta, Alonso, Carmen, Barragán, Eva, Gómez Seguí, Inés, Neef, Alexandre, Hervás Marín, David, Montesinos, Pau, Sanz, Guillermo, Sanz, Miguel Ángel, Dopazo, Joaquín, Cervera, José
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad Católica de Valencia San Vicente Mártir
Repositorio:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
Idioma:inglés
OAI Identifier:oai:riucv.ucv.es:20.500.12466/3894
Acceso en línea:http://hdl.handle.net/20.500.12466/3894
Access Level:acceso abierto
Palabra clave:Acute myeloid leukemia (AML)
Genetic
Mutation
2410 Biología Humana
2414 Microbiología
3205.04 Hematología
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spelling The modular network structure of the mutational landscape of Acute Myeloid LeukemiaIbáñez, MariamCarbonell Caballero, JoséSuch, EsperanzaGarcía Alonso, LuzLiquori, AlessandroLópez Pavía, MaríaLlop, MartaAlonso, CarmenBarragán, EvaGómez Seguí, InésNeef, AlexandreHervás Marín, DavidMontesinos, PauSanz, GuillermoSanz, Miguel ÁngelDopazo, JoaquínCervera, JoséAcute myeloid leukemia (AML)GeneticMutation2410 Biología Humana2414 Microbiología3205.04 HematologíaAcute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways.20242024-01-3120182018-10-1020182018-10-10journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12466/3894reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártirinstname:Universidad Católica de Valencia San Vicente MártirInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:riucv.ucv.es:20.500.12466/38942026-06-19T08:32:07Z
dc.title.none.fl_str_mv The modular network structure of the mutational landscape of Acute Myeloid Leukemia
title The modular network structure of the mutational landscape of Acute Myeloid Leukemia
spellingShingle The modular network structure of the mutational landscape of Acute Myeloid Leukemia
Ibáñez, Mariam
Acute myeloid leukemia (AML)
Genetic
Mutation
2410 Biología Humana
2414 Microbiología
3205.04 Hematología
title_short The modular network structure of the mutational landscape of Acute Myeloid Leukemia
title_full The modular network structure of the mutational landscape of Acute Myeloid Leukemia
title_fullStr The modular network structure of the mutational landscape of Acute Myeloid Leukemia
title_full_unstemmed The modular network structure of the mutational landscape of Acute Myeloid Leukemia
title_sort The modular network structure of the mutational landscape of Acute Myeloid Leukemia
dc.creator.none.fl_str_mv Ibáñez, Mariam
Carbonell Caballero, José
Such, Esperanza
García Alonso, Luz
Liquori, Alessandro
López Pavía, María
Llop, Marta
Alonso, Carmen
Barragán, Eva
Gómez Seguí, Inés
Neef, Alexandre
Hervás Marín, David
Montesinos, Pau
Sanz, Guillermo
Sanz, Miguel Ángel
Dopazo, Joaquín
Cervera, José
author Ibáñez, Mariam
author_facet Ibáñez, Mariam
Carbonell Caballero, José
Such, Esperanza
García Alonso, Luz
Liquori, Alessandro
López Pavía, María
Llop, Marta
Alonso, Carmen
Barragán, Eva
Gómez Seguí, Inés
Neef, Alexandre
Hervás Marín, David
Montesinos, Pau
Sanz, Guillermo
Sanz, Miguel Ángel
Dopazo, Joaquín
Cervera, José
author_role author
author2 Carbonell Caballero, José
Such, Esperanza
García Alonso, Luz
Liquori, Alessandro
López Pavía, María
Llop, Marta
Alonso, Carmen
Barragán, Eva
Gómez Seguí, Inés
Neef, Alexandre
Hervás Marín, David
Montesinos, Pau
Sanz, Guillermo
Sanz, Miguel Ángel
Dopazo, Joaquín
Cervera, José
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Acute myeloid leukemia (AML)
Genetic
Mutation
2410 Biología Humana
2414 Microbiología
3205.04 Hematología
topic Acute myeloid leukemia (AML)
Genetic
Mutation
2410 Biología Humana
2414 Microbiología
3205.04 Hematología
description Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-10-10
2018
2018-10-10
2024
2024-01-31
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12466/3894
url http://hdl.handle.net/20.500.12466/3894
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 4.0 Internacional
http://creativecommons.org/licenses/by/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 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
instname:Universidad Católica de Valencia San Vicente Mártir
instname_str Universidad Católica de Valencia San Vicente Mártir
reponame_str RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
collection RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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