融合基因是指两个独立基因的编码区首尾相连所形成的且置于同一套调控序列控制的产物,研究表明许多癌症的发生与融合基因存在密切的联系。融合基因可作为癌症治疗的靶点,在癌症诊断及治疗领域中融合基因的研究具有重要意义。部分融合基因驱动癌症的机制已被初步揭示,但是有些真实存在的在肿瘤发生发展过程中有重要意义的融合基因由于工具和实验技术限制还未被发现。因此,对融合基因的分析预测研究方法逐渐成为关注的热点之一。本文探讨了目前常用的关于融合基因的分析工具及方法,为融合基因在癌症中的研究提供思路。

Fusion genes are the products of two independent genes whose coding regions are linked and controlled by the same set of regulatory sequences．Studies have shown that many cancers are closely linked to gene fusions．Fusion genes can be used as targets for cancer therapy,and the study of fusion genes is of great importance in cancer diagnosis and treatment．Some of the mechanisms of fusion genes driving cancer have been initially revealed,but there are more fusion genes which are important in the process of tumor development have not been discovered due to the limitation of tools and experimental techniques．Therefore,the analysis and prediction methods of fusion genes are becoming a hot topic of interest．In this paper,we discuss the commonly used analytical tools and methods on fusion genes to provide ideas for the study of fusion genes in cancer．

目的 通过对43种融合基因在儿童白血病中的结果分析,探讨融合基因阳性的儿童急性B淋巴细胞白血病(acute B-lymphoblastic leukemia,B-ALL)的免疫表型特征。方法 应用实时荧光探针PCR法对2016年10月—2018年12月在深圳市儿童医院就诊的初发或复发B-ALL患儿进行融合基因检测,采用多参数流式细胞术(flow cytometry,FCM)对B-ALL患者进行免疫表型检测。结果 120例B-ALL患儿融合基因筛选总阳性率为37.5%(45/127),包括TEL/AML1 27例、E2 A/PBX1 7例、BCR/ABL1 6例、MLL 4例、TLS/ERG 1例;不同年龄段白血病融合基因阳性率差异有统计学意义(P<0.01),性别分布差异无统计学意义(P>0.05)。各融合基因阳性组CD19阳性率为100%,TEL/AML1阳性表达患者普通-B-ALL表型占比最高(77.8%),干/祖细胞抗原CD34的阳性率为81.5%;E2 A/PBX1阳性表达患者以前-B-ALL表型为主,不表达已知的T系及髓系抗原;各融合基因阳性组及阴性组患儿髓系抗原阳性率比较差异有统计学意义(P<0.01),以BCR/ABL1基因表达组阳性率最高(100%)。结论 5种融合基因在患者年龄构成及免疫表型中具有一定的分布特点;B-ALL特征性免疫表型的改变可用于融合基因表达的预测,提高融合基因结果判读的准确率。

Objective To investigate the immunophenotype features of children with acute B-lymphoblastic leukemia(B-ALL) combined with fusion gene expressing after to analyze the results of the 43 fusion genes. Methods Real-time fluorescent probe PCR assay was used for the detection of fusion genes in 120 cases of children from Shenzhen Children's Hospital with B-ALL newly or recurrently diagnosed from Oct 2016 to Dec 2018. Multi-parameter flow cytometry(FCM) was used for the detection of the immunophenotype in children with B-ALL. Results Of all the 120 cases, the fusion genes were detected at positive rate of 37.5%(45/120), included TEL/AML1 27 cases, E2 A/PBX1 7 cases, BCR/ABL1 6 cases, MLL 4 cases, TLS/ERG 1 cases. The positive rate of leukemia fusion gene had statistically difference among fusion genes positive groups based on age(P<0.01). There was no statistically difference in the gender distribution(P>0.05). The expressing of CD19 was at positive rate of 100% in all of the groups. The rate of the common-B-ALL was the highest B-ALL subtype in the TEL/AML1 positive groups(77.8%). The stem /progenitor associated antigen CD34 was at positive rate of 81.5%. The pre-B-ALL was the main subtype in the E2 A/PBX1 group, which was no expression of the known T-ALL associated antigen MyAg antigen. There was statistically difference in the positive rate of MyAg expression among all of the groups(P<0.01), with the highest rate in the BCR/ABL1 group(100%). Conclusion There were certain distribution features in age composition and immunophenotype of children with B-ALL carrying five kinds of common fusion genes. The characteristic changes of the immunophenotype of B-ALL may be used to predict the expression of fusion genes and improve the accuracy of fusion genes by the supplementary role of immunophenotype analysis.