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...
| Autores: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
|---|---|
| Tipo de documento: | Artigo |
| Data de publicação: | 2018 |
| País: | España |
| Recursos: | Universidad Católica de Valencia San Vicente Mártir |
| Repositório: | RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir |
| Idioma: | Inglês |
| OAI Identifier: | oai:riucv.ucv.es:20.500.12466/3894 |
| Acesso em linha: | http://hdl.handle.net/20.500.12466/3894 |
| Nível de acesso: | Acesso aberto |
| Palavra-chave: | Acute myeloid leukemia (AML) Genetic Mutation 2410 Biología Humana 2414 Microbiología 3205.04 Hematología |
| _version_ | 1878741236778532864 |
|---|---|
| author | Ibáñez, Mariam |
| 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 |
| author_browse | Alonso, Carmen Barragán, Eva Carbonell Caballero, José Cervera, José Dopazo, Joaquín García Alonso, Luz Gómez Seguí, Inés Hervás Marín, David Ibáñez, Mariam Liquori, Alessandro Llop, Marta López Pavía, María Montesinos, Pau Neef, Alexandre Sanz, Guillermo Sanz, Miguel Ángel Such, Esperanza |
| 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 |
| collection | RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_e19b7c4875fe4f8eeee0da3ea71e484c |
| institution | Universidad Católica de Valencia San Vicente Mártir |
| instname_str | Universidad Católica de Valencia San Vicente Mártir |
| language | eng |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:riucv.ucv.es:20.500.12466/3894 |
| publishDate | 2018 |
| publishDateSort | 2018 |
| reponame_str | RIUCV. Repositorio de la Universidad Católica de Valencia San Vicente Mártir |
| spelling | The modular network structure of the mutational landscape of Acute Myeloid Leukemia 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 Acute myeloid leukemia (AML) Genetic Mutation 2410 Biología Humana 2414 Microbiología 3205.04 Hematología 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. http://hdl.handle.net/20.500.12466/3894 |
| 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 | 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_short | 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 |
| topic | Acute myeloid leukemia (AML) Genetic Mutation 2410 Biología Humana 2414 Microbiología 3205.04 Hematología |
| topic_facet | Acute myeloid leukemia (AML) Genetic Mutation 2410 Biología Humana 2414 Microbiología 3205.04 Hematología |
| url | http://hdl.handle.net/20.500.12466/3894 |