Ph 阴性骨髓增殖性肿瘤患者的基因突变特点

Characterization of mutational pattern in patients with Ph negative myeloproliferative neoplasms

目的：探讨49个髓系肿瘤相关基因在Ph阴性骨髓增殖性肿瘤（ MPN）患者中的突变特点。方法对51例Ph阴性MPN患者的49个髓系肿瘤相关基因的全外显子进行检测。其中CALR（exon9）、NPM1（exon12）和CEBPA（TAD、BZIP两个结构功能域）同时采用Sanger测序法检测， FLT3-ITD采用聚合酶链反应方法检测。结果73.5％（36／49）的基因检测到突变，其中 JAK2-V617F、CALR（ exon9）和 MPL 突变率分别为60.8％（31／51）、7.8％（4／51）和7.8％（4／51）；此外ASXL1、SETBP1和SF3B13个基因的突变率均大于10％。96.1％（49／51）的患者被检测到突变，且以携带3个和4个突变的患者最多，占52.9％（27／51）；JAK2-V617F阳性患者的基因突变数量明显多于JAK2-V617F和CALR（exon9）双阴性患者（P＜0.05）；真性红细胞增多症、原发性骨髓纤维化、原发性血小板增多症和骨髓增殖性肿瘤，未分类型之间的基因突变数量差异无统计学意义（ P＞0.05）。结论大多数的Ph阴性MPN患者携带≥3个基因突变，且不同的MPN患者具有不同的基因突变特点。

Objective To characterize the molecular profile in patients with Ph negative myeloproliferative neoplasms （ MPN） by exploring 49 gene mutations.Methods Targeted gene sequencing were performed to analyze 49 MPN-associated genes in 51 patients with Ph negative MPN, of which CARL （ exon 9 ） , NPM1 （ exon 12 ） and CEBPA （ TAD, BZIP domains ） were investigated by using Sanger sequencing simultaneously, while FLT3-ITD was assessed by PCR method. Results Mutations were detected in 73.5%（36/49） of genes, and the mutational rates of JAK2-V617F, CALR （exon 9） and MPL were 60.8%（ 31/51 ） , 7.8%（ 4/51 ） and 7.8%（ 4/51 ） respectively, whereas the mutational rates of ASXL1, SETBP1, and SF3B1 were around 10%.In addition, 96.1%（49/51） of patients harbored at least one mutation, and more than half of the patients （52.9%,27/51） possessed 3 or 4 gene mutations.The amount of gene mutations was significantly higher in patients with JAK2-V617F mutation than those without JAK2-V617F or CALR （exon 9） mutation （P〈0.05）.The last finding was that there was no statistically significant difference in the amount of mutations among four MPN subtypes （ PV, ET, PMF, and MPN-U） . Conclusion Most patients with Ph negative MPN possesses three or more gene mutations, with various mutational profiles.