FANCJ基因在成人急性髓系白血病中的突变图谱

Mutation Spectrum of FANCJ Gene in Adult Acute Myeloid Leukemia

目的:检测分析急性髓系白血病(acute myeloid leukemia, AML)患者FANCJ基因突变情况,为研究FANCJ突变类型的AML疾病致病机理奠定基础,同时为其疾病防治提供指导。方法:在FANCJ基因蛋白编码区设计引物,采用PCR扩增及sanger测序法检测222例初诊AML患者骨髓细胞中FANCJ基因编码区突变情况,同时检测AML患者黏膜上皮组织FANCJ基因突变情况;采用NCBI Blast在线生物信息学软件分析FANCJ基因突变在不同物种中的进化保守性。结果:测序分析显示,FANCJ基因在蛋白编码区的11个位点出现突变,分别为exon5:c.G430A:p.A144T,exon6:c.A587G:p.N196S,exon9:c.C1255T:p.R419W,exon10:c.G1442A:p.G481D,exon11:c.C1609G:p.L537V,exon16:c.C2360T:p.P787L,exon17:c.C2440T:p.R814C,exon19:c.C2608T:p.H870Y,exon19:c.A2686G:p.I896V,exon19:c.C2830G:p.Q944E,exon20:c.G3412A:p.D1138N,其中A144T、N196S、R814C、I896V及Q944E突变存在复现性;另外,A144、R419、G381、L537、P787、H870、Q944及D1138位点在不同物种中高度保守。结论:在222例AML患者中发现26名患者中存在FANCJ突变,并且突变位点在不同物种中相对保守,功能重要,这为接下来研究FANCJ突变类型的AML疾病致病机理奠定基础,同时为疾病防治提供指导。

Objective:To detect and analyze the mutation status of FANCJ gene in adult AML patients,so as to provide the basis for studying the mechanism of FANCJ driven AML and guiding the preventim and treatment of deseese.Methods:The cDNAs were extracted and transeripted from bone marrow cells and normal skin cells in 222 newly diagnosed AML patients.The primers were designed for FANCJ gene coding region,the mutations of FANCJ gene coding region in AML patients as well as the mutations of FANCJ gene in mucous membrane epethelia in patients were detected by PCR and sanger seguencing;the evolutionary conservation of FANCJ mutation in different organisms was analyzed by NCBI Blast online bioinformaties software.Results:The sequencing analysis showed that the mutations of FANCJ gene happened in 11 sites of FANCJ gene coding region,which were as followed:exon5:c.G430 A:p.A144 T,exon6:c.A587 G:pN196 S,exon9:c.C1255 T:p.R419 W,exon10:c.G1442 A:p.G481 D,exon11:c.C1609 G:p.L537 V,exon16:c.C2360 T:p.P787 L,exon17:c.C2440 T:p.R814 C,exon19:c.C2608 T:pH870 Y,exon19:c.A2686 G:p.I896 V,exon19:c.C2830 G:p.Q944 E,exon20:c.G3412 A:p.D1138 N.Among them,the repeatability existed in mutations of A144 T,N196 S,R814 C,I896 V and Q944 E.Beside,the mutation sites of A144,R419,G381,L537,P787,H870,Q944 and D1138 were highly conserved in different organisms.Conclusion:Among 222 adult AML patients,the mutations of FANCJ gene have been found in 26 patients,moreover,the mutation sites are relatively conserved in different organisms,and possess important fanction.The results of this study provide the basis for exploring the mexhanism of FANCJ gene driven AML and for guiding the prevantion and treatment of AML.