摘要
目的分析儿童急性淋巴细胞白血病(ALL)的基因突变谱及其预后意义。方法回顾性分析2016年11月至2019年12月福建医科大学附属协和医院采用二代测序技术(NGS)行基因突变检测的141例初治ALL患儿的临床资料,分析基因突变谱及其对ALL患儿预后的影响。结果141例患儿中,83例(58.9%)检出体细胞突变,包括37个Ⅰ类及123个Ⅱ类突变位点。单核苷酸变异(SNV)为最常见的突变类型。KRAS(20/160,12.5%)为最常见的突变基因,其次为NOTCH1(11.9%)及NRAS(10.6%)。RAS通路(KRAS、FLT3、PTPN11)、PAX5及TP53突变仅在B-ALL患儿中检出,而FBXW7、PTEN突变仅在T-ALL患儿中检出;NRAS突变主要在B-ALL中检出,而NOTCH1突变主要在T-ALL中检出。每例T-ALL患儿检出的平均基因突变个数显著高于B-ALL患儿(4.16±1.33对2.04±0.92,P=0.004)。按照有无遗传变异将患儿分为突变组和无突变组,两组的性别、年龄、初诊白细胞计数、微小残留病监测结果、预计3年无事件生存(EFS)率及总生存(OS)率差异均无统计学意义(P值均>0.05);但突变组T-ALL以及融合基因阴性患儿的比例显著高于无突变组(P值分别为0.021和<0.001)。进一步亚组分析,在融合基因阴性的患儿中,有Ⅰ类突变的患儿预计3年EFS率显著低于无Ⅰ类突变的患儿(85.5%对100.0%,P=0.039);在B-ALL患儿中,伴TP53突变的患儿预计3年EFS率显著低于不伴有TP53突变的患儿(37.5%对91.2%,P<0.001)。结论体细胞突变在儿童ALL中较为常见,与临床表型及预后具有一定的相关性,NGS可作为传统MICM分型检查的重要补充。
Objective This study analyzed the correlation between genetic mutation and prognostic significance in childhood acute lymphoblastic leukemia(ALL).Methods Targeted exome by next-generation sequencing(NGS)technology was used to carry out molecular profiling of untreated 141 children with ALL in Fujian Medical University Union Hospital from November 2016 to December 2019.Correlation of genetic features and clinical features and outcomes was analyzed.Results Among the 141 pediatric patients with ALL,160 somatic mutations were detected in 83 patients(58.9%),including 37 gradeⅠmutations and 123 gradeⅡmutations.Single nucleotide variation was the most common type of mutation.KRAS was the most common mutant gene(12.5%),followed by NOTCH1(11.9%),and NRAS(10.6%).RAS pathway(KRAS,FLT3,PTPN11),PAX5 and TP53 mutations were only detected,and NRAS mutations was mainly found in B-ALL while FBXW7 and PTEN mutations were only found,and NOTCH1 mutation was mainly detected in T-ALL.The average number of mutations detected in each child with T-ALL was significantly higher than in children with B-ALL(4.16±1.33 vs 2.04±0.92,P=0.004).The children were divided into mutation and non-mutation groups according to the presence or absence of genetic variation.There were no statistically significant differences in sex,age,newly diagnosed white blood cell count,minimal or measurable residual disease monitoring results,expected 3-year event-free survival(EFS)and overall survival(OS)between the two groups(P>0.05).On the other hand,the proportion of T-ALL and fusion gene negative children in the mutant group was significantly higher than the non-mutation group(P=0.021 and 0.000,respectively).Among the patients without fusion gene,the EFS of children with grade I mutation was significantly lower than children without grade I mutation(85.5%vs 100.0%,P=0.039).Among children with B-ALL,the EFS of those with TP53 mutation was significantly lower than those without TP53 mutation(37.5%vs 91.2%,P<0.001).Conclusion Genetic variation is more common in childhood ALL and has a certain correlation with clinical phenotype and prognosis.Therefore,targeted exome by NGS can be used as an important supplement to the traditional morphology,immunology,cytogenetics,and molecular biology classification.
作者
郑湧智
郑浩
陈再生
华雪玲
乐少华
李健
胡建达
Zheng Yongzhi;Zheng Hao;Chen Zaisheng;Hua Xueling;Le Shaohua;Li Jian;Hu Jianda(Department of Pediatric Hematology,Fujian Institute of Hematology,Fujian Provincial Key Laboratory,Fujian Medical University Union Hospital,Fuzhou 350001,China;Department of Hematology,Fujian Institute of Hematology,Fujian Provincial Key Laboratory,Fujian Medical University Union Hospital,Fuzhou 350001,China)
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2022年第1期19-25,共7页
Chinese Journal of Hematology
基金
福建省血液医学中心建设项目(闽政办(2017)4号)
福建医科大学启航基金项目(2019QH1032)。
关键词
白血病
淋巴细胞
急性
基因突变
二代测序
儿童
Leukemia,lymphoblastic,acute
Genetic muation
Next-generation sequencing
Child
