Research Papers:

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

Yuanyuan Xu, Yan Li, Qingyu Xu, Yuelong Chen, Na Lv, Yu Jing, Liping Dou, Jian Bo, Guangyuan Hou, Jing Guo, Xiuli Wang, Lili Wang, Yonghui Li, Chongjian Chen and Li Yu _

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Oncotarget. 2017; 8:82475-82490. https://doi.org/10.18632/oncotarget.19628

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Yuanyuan Xu1,2,*, Yan Li1,2,*, Qingyu Xu1,3,*, Yuelong Chen4, Na Lv1, Yu Jing1, Liping Dou1, Jian Bo1, Guangyuan Hou4, Jing Guo4, Xiuli Wang4, Lili Wang1, Yonghui Li1, Chongjian Chen4 and Li Yu1,5

1Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing 100853, China

2Department of Hematology, Hainan Branch of Chinese PLA General Hospital, Sanya 572013, Hainan Province, China

3Medical school of Nankai University, Tianjin 300071, China

4Annoroad Gene Technology Co. Ltd, Beijing 100176, China

5Department of Hematology, General Hospital of Shenzhen University, Shenzhen 518060, China

*These authors have contributed equally to this work

Correspondence to:

Li Yu, email: [email protected]

Keywords: myelodysplastic syndromes, mutational spectrum, next-generation sequencing, risk stratification

Received: May 10, 2017     Accepted: June 30, 2017     Published: July 27, 2017


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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