RT Journal
A1 Bao, Zhao-Shi
A1 Chen, Hui-Min
A1 Yang, Ming-Yu
A1 Zhang, Chuan-Bao
A1 Yu, Kai
A1 Ye, Wan-Lu
A1 Hu, Bo-Qiang
A1 Yan, Wei
A1 Zhang, Wei
A1 Akers, Johnny
A1 Ramakrishnan, Valya
A1 Li, Jie
A1 Carter, Bob
A1 Liu, Yan-Wei
A1 Hu, Hui-Min
A1 Wang, Zheng
A1 Li, Ming-Yang
A1 Yao, Kun
A1 Qiu, Xiao-Guang
A1 Kang, Chun-Sheng
A1 You, Yong-Ping
A1 Fan, Xiao-Long
A1 Song, Wei Sonya
A1 Li, Rui-Qiang
A1 Su, Xiao-Dong
A1 Chen, Clark C.
A1 Jiang, Tao
T1 RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas
JF Genome Research 
JO Genome Research 
YR 2014 
FD November 01 
VO 24 
IS 11 
SP 1765 
OP 1773 
DO 10.1101/gr.165126.113 
UL http://genome.cshlp.org/content/24/11/1765.abstract 
AB Studies of gene rearrangements and the consequent oncogenic fusion proteins have laid the foundation for targeted cancer therapy. To identify oncogenic fusions associated with glioma progression, we catalogued fusion transcripts by RNA-seq of 272 gliomas. Fusion transcripts were more frequently found in high-grade gliomas, in the classical subtype of gliomas, and in gliomas treated with radiation/temozolomide. Sixty-seven in-frame fusion transcripts were identified, including three recurrent fusion transcripts: FGFR3-TACC3, RNF213-SLC26A11, and PTPRZ1-MET (ZM). Interestingly, the ZM fusion was found only in grade III astrocytomas (1/13; 7.7%) or secondary GBMs (sGBMs, 3/20; 15.0%). In an independent cohort of sGBMs, the ZM fusion was found in three of 20 (15%) specimens. 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.