大量肿瘤中都存在着DNA甲基化改变情况，DNA 甲基转移酶3B（DNMT3B）主要功能是DNA甲基化的从头合成，其在肿瘤DNA甲基化变化中有重要作用。DNMT3B 到目前为止有40多种异构体，其中有7种主要的异构体，人们虽然对DNMT3B在肿瘤发生发展中的作用做了大量研究，但DNMT3B的异构体在肾癌发生发展中的作用尚未见报道，据此，有必要对其进行深入研究。本课题拟以肾癌临床样本、稳定表达DNMT3B异构体的肾癌细胞株和种植到裸鼠肾脏部位稳定表达DNMT3B异构体细胞株后形成的肿瘤为研究材料，检测其中DNMT3B主要异构体的表达情况及RASSF1A等抑癌基因甲基情况，同时利用二代测序技术高通量分析基因启动区甲基化的变化，并研究稳定表达DNMT3B异构体细胞株的增殖情况及裸鼠肾脏移植细胞后肿瘤大小等指标。通过临床样本、细胞实验和实验动物来探明DNMT 3B异构体在肾癌发生发展中的作用。

Alterations in DNA methylation have been associated with genome-wide hypomethylation and specific gene hypermethylation in numerous cancers. DNA methyltransferase(DNMT) 3B is critical for de novo DNA methylation and play an important role in tumorigenesis. Nearly 40 different DNMT3B isoforms,including 7 types major isoforms, generated by alternative splicing and/or alternative promoter usage have been reported. Although a lot of studies reported that aberrant overexpression DNMT3B strong links to cancer, the functions of DNMT3B isoforms in renal cell carcinoma(RCC) is still unclear. So it is necessary to study the role of DNMT3B isoforms in RCC.The clinical RCC sample, stable renal cell line which overexpress DNMT3B isoforms, tumor xenografts which from overexpression DNMT3B isoforms stable renal cell line, will be used in this study.The mRNA and protein levels of DNMT3B isoforms and of some tumor suppressor gene,the global methylation and specific gene methylation will be measured using these 3 kinds of samples. At the same time, the High-throughput sequencing technique will be used to reveal the state of promoter methylation of whole genomic DNA of 3 kinds of samples. The proliferation of renal cell which overexpress DNMT3B isoforms and the tumor size of tumor xenografts in nude mice and so on will be measured. In conclusions, the role of DNMT3B isoforms in tumorigenesis in RCC will be claritied using clinical sample,cell level and laboratory animal.