Objective: To clarify the prevalence, clinical features and molecular characteristics of germline GATA2 mutations in pediatric primary myelodysplastic syndromes (MDS) . Methods: Next-generation sequencing technology was used to detect mutations in GATA2 and other myeloid malignancy genes in 129 children with primary MDS from Jan. 2007 to Jan. 2018. The relationship between genotypes and phenotypes was analyzed. Results: Germline GATA2 mutations accounted for 8.5% (11/129) of all primary MDS cases, and 14.0% (11/50) of MDS with excess blasts (MDS-EB) and acute myeloid leukaemia with myelodysplasia-related changes (AML-MRC) . Compared with GATA2 wild-type patients, GATA2 mutated patients were older at diagnosis[8 (1-16) years old vs 6 years old (range: 1 month old-18 years old) , P=0.035]and higher risk of monosomy 7 (72.7%vs 5.2%, P<0.001) and classified into MDS-EB and AML-MRC compared with refractory cytopenia of childhood (RCC) (63.6%vs 36.4%, P=0.111) . The multivariate analysis showed SETBP1 mutation (P=0.041, OR=9.003, 95%CI 1.098-73.787) and isolated monosomy 7 (P=0.002, OR=24.835, 95%CI 3.305-186.620) were significantly associated with germline mutated GATA2. Overall survival (OS) and outcomes of hematopoietic stem cell transplantation (HSCT) were not influenced by GATA2 mutational status. Conclusions: Our data identify germline GATA2 mutations have a high prevalence in older pediatric patients with monosomy 7, and high risk of progression into advanced MDS subtypes. GATA2 mutation status does not affect OS in pediatric primary MDS.
目的： 探讨我国GATA2突变相关儿童原发性骨髓增生异常综合征（MDS）的发生情况、临床特点及分子生物学特征。 方法： 回顾性分析2007年1月至2018年1月129例儿童原发性MDS患者临床资料，采用二代测序技术检测GATA2及髓系恶性肿瘤相关基因突变情况。分析基因突变谱及其与临床表现型的关系。 结果： 在所有129例患者中，11例（8.5%）检出GATA2胚系突变。在50例MDS伴原始细胞增高（MDS-EB）和急性髓系白血病伴MDS相关改变（AML-MRC）患者中，GATA2胚系突变占14.0%。GATA2突变多位于第二个锌指（ZF2）区。多因素分析结果显示，SETBP1体细胞突变（P=0.041，OR=9.003，95%CI 1.098~73.787）和独立的7号染色体单体（P=0.002，OR=24.835，95%CI 3.305~186.620）与GATA2胚系突变显著相关。与GATA2野生型的患者相比，GATA2突变型患者中位发病年龄更大[8（1~16）岁对6岁（1月龄~18岁），P=0.035]，更易伴有7号染色体单体（72.7%对5.2%，P<0.001），较之儿童难治性血细胞减少（RCC）更倾向于存在于MDS-EB/AML-MRC亚型中（5.1%对13.7%，P=0.111）。GATA2突变与否不影响儿童原发性MDS患者的3年预期总生存（OS）率[（80.1±4.2）%对（60.6±25.4）%，P=0.437]；在44例接受allo-HSCT患者中，GATA2突变与否对移植后3年预期OS率无显著影响[100.0%对（94.0±3.8）%，P=0.562]。 结论： GATA2突变在我国伴有7号染色体单体及年龄较大的儿童原发性MDS患者中占有较高的比例，且GATA2突变患者多进展为MDS-EB和AML-MRC。GATA2突变状态不影响儿童原发性MDS的总体生存。.
Keywords: GATA2 mutation; Germline; Myelodysplastic syndrome; Pediatric.