利用微阵列比较基因组杂交技术检测多发性骨髓瘤的遗传学异常  

Detection of the Cytogenetic Aberrations in Multiple Myeloma by Using Microrray Comparative Genomic Hybridization

作　　者：王艳芳[1] 王化[1] 郤连永 张朕豪 王晶[1] 董菲[1] 克晓燕[1] WANG Yan-Fang;WANG Hua;XI Lian-Yong;ZHANG Zhen-Hao;WANG Jing;DONG Fei;KE Xiao-Yan(Department of Hematology,Peking University Third Hospital,Beijing 100191,China)

机构地区：[1]北京大学第三医院血液科,北京100191

出　　处：《中国实验血液学杂志》2018年第5期1389-1395,共7页Journal of Experimental Hematology

摘　　要：目的:利用微阵列比较基因组杂交技术分析初诊多发性骨髓瘤(MM)患者的遗传学异常,探讨其在MM遗传学异常检测中的应用价值。方法:对20例初发MM患者,利用CytoScan 750K芯片对其骨髓细胞进行全基因组拷贝数变异分析;另外通过骨髓细胞染色体核型分析及利用多个荧光探针(D13S319、RB1、p53、1q21、IgH、IgH/CCND1、IgH/FGFR3、IgH/MAF、IgH/MAFB)FISH检测骨髓细胞的染色体异常。结果:20例MM患者中,染色体核型异常者3例(15%);FISH检测染色体异常13例(65%),而芯片检出18例(90%)患者具有染色体拷贝数异常(CNV),包括拷贝数增加(106个)、拷贝数缺失(156个)以及单亲二倍体(23个),除了5号、9号、18号、21号以及Y染色体未发现CNV外,其余染色体上均包含不同数量的拷贝数增加和/或缺失。FISH和芯片检测比较显示,13号染色体缺失(D13S319、RB1)发生率分别为35%(7/20)和40%(8/20);1q21扩增分别为40%(8/20)和50%(10/20);P53缺失均为15%(3/20);FISH检出IgH重排阳性8例,芯片检出4例11q13(CCND1基因)扩增,3例16q23(MAF基因)扩增,1例4p16(FGFR3基因)扩增,2例20q12(MAFB基因)扩增。另外,芯片还可以发现了新的如7号、8号、12号、X等染色体异常。结论:半数以上MM患者都存在染色体改变,而且大部分均为复杂异常,利用微阵列芯片可以提高染色体异常的检出率,为MM预后判断提供更多的分子遗传学信息。Objective:To detect the molecular cytogenetic abnormalities of multiple myeloma(MM)by using microrraybased comparative genomic hybridization(array-CGH)technology and to investigate its value of application in MM.Methods:The whole-genoine copy number variants(CNV)of bone marrow samples acquired from 20 cases of newly diagnosed MM patients were detected by genome-wide hybridization and scanning by CytoScan 750K Array(Affymetrix).At the same time,the chromosome abnormalities of bone marrow cells were detected by karyotype analysis and FISH using 9 specific probes:D13S319,RB1,p53,1q21,IgH,IgH/CCND1,IgH/FGFR3,IgH/MAF,IgH/MAFB.Results:Among the 20 MM patients,the incidence of chromosome abnormalities detected by karyotype analysis,FISH and array-CGH were 15%,65%and 90%,respectively.The types of CNV detected by array-CGH included the gain(106),loss(156)or UPD(23).There were many different CNVs in every chromosomes except chromosome 5,9,18,21 and Y.Comparison of chromosome abnormalities detected by FISH and array-CGH showed that,the positive ratio of del(13q)was 35%and 40%respectively;the positive ratio of amp(1q)was 40%and 50%respectively;the positive ratio of del(17p)was both 15%.FISH detection showed 8 cases with IgH rearrangement,meansahile the array-CGH detection showed that 4 cases had amp(11q13)(CCND1 gene),3 cases had amp(16q23)(MAF gene),1 case had amp(4p16)(FGFR3 gene)and 2 cases had amp(20q12)(MAFB gene).Besides,many other new chromosome abnormalities were found.Conclusion:More than half of MM patients have cytogenetic changes,and most of them are complex chromosomal abnormalities.By using array-CGH,more chromosome abnormalities can be detected and more cytogenetic information can be provided for clinician.

关 键 词：多发性骨髓瘤 染色体异常 微阵列比较基因组杂交 荧光原位杂交 

分 类 号：R733.3[医药卫生—肿瘤]