二代测序技术(NGS)检测儿童急性淋巴细胞白血病的基因突变谱及预后分析

Detection of gene mutation profile and prognostic analysis in children with acute lymphoblastic leukemia by second generation sequencing technique(NGS)

目的研究分析儿童急性淋巴细胞白血病(ALL)运用二代测序技术(NGS)检测的基因突变谱及预后意义。方法选择2019年1月-2021年12月北京高博博仁医院收治的急性淋巴细胞白血病患儿400例为研究对象,运用NGS检测基因突变情况,总结分析患儿基因突变谱及预后。结果400例患儿中,检出体细胞突变235例,以单核苷酸变异为主要突变类型,最常见的突变基因为KRAS,其次为NOTCH1、NRAS。RAS通路、TP53、PAX5突变基因只在B-ALL患儿中检出,PTEN、FBXW7突变基因只在T-ALL患儿中检出;B-ALL患儿检出突变基因主要为NRAS,T-ALL患儿检出突变基因主要为NOTCH1。B-ALL患儿检出突变基因的平均数少于T-ALL患儿(P<0.05)。根据是否有遗传变异将患儿分成无突变组与突变组,在性别、年龄、初诊白细胞计数、染色体核型方面,两组比较,不存在统计学差异(P>0.05);在融合基因方面,两组对比存在统计学差异(P<0.05)。结论在ALL患儿中,体细胞突变是一种比较常见的突变类型,与临床表型、预后有着一定的关系,可将NGS看作是MICM分型检查的一项补充。

Objective To study and analyze the gene mutation spectrum detected by second generation sequencing technology(NGS)in children with acute lymphoblastic leukemia(ALL)and its prognostic significance.Methods 400 children with acute lymphoblastic leukemia admitted to our hospital from January 2019 to December 2021 were selected as the study objects.NGS was used to detect gene mutation,and the gene mutation spectrum and prognosis of children were summarized and analyzed.Results Among 400 children,235 somatic mutations were detected.The single nucleotide mutation was the main type of mutation.The most common mutation gene was KRAS,followed by NOTCH1 and NRAS.RAS pathway,TP53,PAX5 mutation genes were only detected in B-ALL children,PTEN,FBXW7 mutation genes were only detected in T-ALL children;the mutation gene detected in children with B-ALL is mainly NRAS,and the mutation gene detected in children with T-ALL is mainly NOTCH1.The average number of mutation genes detected in children with B-ALL was less than that in children with T-ALL(P<0.05).According to whether there is genetic variation,the children were divided into non mutation group and mutation group.In terms of gender,age,white blood cell count at first diagnosis,and chromosome karyotype,there was no statistical difference between the two groups(P>0.05);in terms of fusion genes,there was a statistical difference between the two groups(P<0.05).Conclusion Somatic mutation is a common mutation type in children with ALL,which has a certain relationship with clinical phenotype and prognosis.NGS can be regarded as a supplement to MICM typing.