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Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing

Myelodysplastic syndromes (MDS) are a group of myeloid hematological malignancies, with a high risk of progression to acute myeloid leukemia (AML). To explore the role of acquired mutations in MDS, 111 MDS-associated genes were screened using next-generation sequencing (NGS), in 125 patients. One or...

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Autores principales: Xu, Yuanyuan, Li, Yan, Xu, Qingyu, Chen, Yuelong, Lv, Na, Jing, Yu, Dou, Liping, Bo, Jian, Hou, Guangyuan, Guo, Jing, Wang, Xiuli, Wang, Lili, Li, Yonghui, Chen, Chongjian, Yu, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669905/
https://www.ncbi.nlm.nih.gov/pubmed/29137279
http://dx.doi.org/10.18632/oncotarget.19628
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author Xu, Yuanyuan
Li, Yan
Xu, Qingyu
Chen, Yuelong
Lv, Na
Jing, Yu
Dou, Liping
Bo, Jian
Hou, Guangyuan
Guo, Jing
Wang, Xiuli
Wang, Lili
Li, Yonghui
Chen, Chongjian
Yu, Li
author_facet Xu, Yuanyuan
Li, Yan
Xu, Qingyu
Chen, Yuelong
Lv, Na
Jing, Yu
Dou, Liping
Bo, Jian
Hou, Guangyuan
Guo, Jing
Wang, Xiuli
Wang, Lili
Li, Yonghui
Chen, Chongjian
Yu, Li
author_sort Xu, Yuanyuan
collection PubMed
description Myelodysplastic syndromes (MDS) are a group of myeloid hematological malignancies, with a high risk of progression to acute myeloid leukemia (AML). To explore the role of acquired mutations in MDS, 111 MDS-associated genes were screened using next-generation sequencing (NGS), in 125 patients. One or more mutations were detected in 84% of the patients. Some gene mutations are specific for MDS and were associated with disease subtypes, and the patterns of mutational pathways could be associated with progressive MDS. The patterns, frequencies and functional pathways of gene mutations are different, but somehow related, between MDS and AML. Multivariate analysis suggested that patients with ≥ 2 mutations had poor progression-free survival, while GATA1/GATA2, DNMT3A and KRAS/NRAS mutations were associated with poor overall survival. Based on a novel system combining IPSS-R and molecular markers, these MDS patients were further divided into 3 more accurate prognostic subgroups. A panel of 11 target genes was proposed for genetic profiling of MDS. The study offers new insights into the molecular signatures of MDS and the genetic consistency between MDS and AML. Furthermore, results indicate that MDS could be classified by mutation combinations to guide the administration of individualized therapeutic interventions.
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spelling pubmed-56699052017-11-09 Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing Xu, Yuanyuan Li, Yan Xu, Qingyu Chen, Yuelong Lv, Na Jing, Yu Dou, Liping Bo, Jian Hou, Guangyuan Guo, Jing Wang, Xiuli Wang, Lili Li, Yonghui Chen, Chongjian Yu, Li Oncotarget Research Paper Myelodysplastic syndromes (MDS) are a group of myeloid hematological malignancies, with a high risk of progression to acute myeloid leukemia (AML). To explore the role of acquired mutations in MDS, 111 MDS-associated genes were screened using next-generation sequencing (NGS), in 125 patients. One or more mutations were detected in 84% of the patients. Some gene mutations are specific for MDS and were associated with disease subtypes, and the patterns of mutational pathways could be associated with progressive MDS. The patterns, frequencies and functional pathways of gene mutations are different, but somehow related, between MDS and AML. Multivariate analysis suggested that patients with ≥ 2 mutations had poor progression-free survival, while GATA1/GATA2, DNMT3A and KRAS/NRAS mutations were associated with poor overall survival. Based on a novel system combining IPSS-R and molecular markers, these MDS patients were further divided into 3 more accurate prognostic subgroups. A panel of 11 target genes was proposed for genetic profiling of MDS. The study offers new insights into the molecular signatures of MDS and the genetic consistency between MDS and AML. Furthermore, results indicate that MDS could be classified by mutation combinations to guide the administration of individualized therapeutic interventions. Impact Journals LLC 2017-07-27 /pmc/articles/PMC5669905/ /pubmed/29137279 http://dx.doi.org/10.18632/oncotarget.19628 Text en Copyright: © 2017 Xu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Xu, Yuanyuan
Li, Yan
Xu, Qingyu
Chen, Yuelong
Lv, Na
Jing, Yu
Dou, Liping
Bo, Jian
Hou, Guangyuan
Guo, Jing
Wang, Xiuli
Wang, Lili
Li, Yonghui
Chen, Chongjian
Yu, Li
Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing
title Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing
title_full Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing
title_fullStr Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing
title_full_unstemmed Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing
title_short Implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing
title_sort implications of mutational spectrum in myelodysplastic syndromes based on targeted next-generation sequencing
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5669905/
https://www.ncbi.nlm.nih.gov/pubmed/29137279
http://dx.doi.org/10.18632/oncotarget.19628
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