Pb2013: the frequency, evolution and significance of gene mutation in myelodysplastic syndromes with normal karyotype

Topic: 10. Myelodysplastic syndromes - Clinical Background: Large-scale sequencing of MDS reveals that gene mutations play important roles in driving the occurrence of MDS, however, little is known about the features of mutations in MDS patients with normal karyotype. Aims: To analyze the gene mutations characteristics and significance for MDS patients with normal karyotype. Methods: 36 genes (high frequency in MDS) were chosen as an assembly to perform the target sequencing for 352 MDS patients with normal chromosome, comparing to 268 cases with abnormal chromosomes. Results: We found that the mutation frequency reached 81.2% for the 352 cases, without difference for the initial mutations (ASXL1, DNMT3A or TET2) when compared to controls. And rare special chromosome-related gene mutations were defined, such as TP53, RUNX1 and U2AF1. Moreover, 20 out of the 352 cases underwent repeated sequencing while the AML transformation did not occur. 14 of them showed mutation evolution, with, or without clinical progression. Finally, 25 MDS/AML (secondary AML) patients accepted paired sequencing analysis between the diagnostic point and immediately after AML transformation. 20 paired samples were defined with newly emerged (15 cases) or existed (5 cases) transformation related mutations (active signaling, transcription factors and tumor suppressor). Summary/Conclusion: High frequency gene mutations, together with the mutation evolution before and after AML transformations, suggested the diagnostic significance of target sequencing for those MDS suspected individual with normal karyotype. The frequency, evolution and significance of gene mutation in myelodysplastic syndromes with normal karyotype *Correspondence to: Xiao Li, MD, PhD, Dept. of Hematology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China. E-mail: [email protected], Tel: +86-021-24058745, F-Fax: +86-021-64701361 This study was supported by the National Natural Science Foundation of China (Grant No. 81770120 and 81770122) The authors declare no competing financial interests. Keywords: MDS, Mutation