国家神经系统疾病临床医学研究中心数据管理与共享系统
Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-METfusion transcript in secondary glioblastomas
基本信息
- 负责人：Zhao-Shi Bao, Hui-Min Chen, Ming-Yu Yang
- 数据来源： OTHERS
- 论文编号：OTHERS20190278
- 发表时间：2014-11-01
2014-11-01
已发表文章
主要研究背景及目的
方法
Clinical specimen collection,RNA-seq and quality control,Read mapping,Hg19 RefSeq (RNA sequences, GRCh37) was downloaded from the UCSC Genome Browser (http://genome.ucsc.edu),Candidate gene fusion identification,Expression analysis of RefSeq genes,RNA extraction and PCR validation,Statistical analysis,Data access.
结论
Our efforts unveiled a novel, recurrent fusion transcript involving the PTPRZ1 and the MET gene (ZM) that was found in 15% of sGBMs. sGBMs harboring this fusion exhibit aggressive clinical behavior and are associated with a poor prognosis for afflicted patients.
主要结果
Genomic analysis revealed that the fusion arose from translocation events involving introns 3 or 8 of PTPRZ and intron 1 of MET. ZM fusion transcripts were found in GBMs irrespective of isocitrate dehydrogenase 1 (IDH1) mutation status. sGBMs harboring ZM fusion showed higher expression of genes required for PIK3CA signaling and lowered expression of genes that suppressed RB1 or TP53 function. Expression of the ZM fusion was mutually exclusive with EGFR overexpression in sGBMs. Exogenous expression of the ZM fusion in the U87MG glioblastoma line enhanced cell migration and invasion. Clinically, patients afflicted with ZM fusion harboring glioblastomas survived poorly relative to those afflicted with non-ZM-harboring sGBMs (P < 0.001). Our study profiles the shifting RNA landscape of gliomas during progression and reveled ZM as a novel, recurrent fusion transcript in sGBMs.