RNA-seq of 272 gliomas revealed a novel, recurrent PTPRZ1-MET fusion transcript in secondary glioblastomas
| Autor: | Kai Yu, Wei Zhang, Chuanbao Zhang, Wan Lu Ye, Chunsheng Kang, Xiao Guang Qiu, Clark C. Chen, Xiao Long Fan, Rui Qiang Li, Wei Yan, Valya Ramakrishnan, Jie Li, Kun Yao, Zhaoshi Bao, Mingyang Li, Hui Min Hu, Wei Sonya Song, Mingyu Yang, Yong ping You, Bo Qiang Hu, Yan Wei Liu, Tao Jiang, Hui Min Chen, Johnny C. Akers, Zheng Wang, Xiao-Dong Su, Bob S. Carter |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male IDH1 Adolescent Oncogene Proteins Fusion Oncogene Proteins Blotting Western Biology Translocation Genetic Young Adult Cell Line Tumor Glioma Temozolomide Genetics medicine Humans neoplasms Antineoplastic Agents Alkylating Genetics (clinical) Aged Brain Neoplasms Receptor-Like Protein Tyrosine Phosphatases Class 5 Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis RNA Research Intron Chemoradiotherapy Middle Aged Proto-Oncogene Proteins c-met medicine.disease Molecular biology Fusion protein Introns Dacarbazine Gene Expression Regulation Neoplastic HEK293 Cells Fusion transcript PTPRZ1 Female Glioblastoma Anaplastic astrocytoma |
| Zdroj: | Genome Research. 24:1765-1773 |
| ISSN: | 1549-5469 1088-9051 |
| DOI: | 10.1101/gr.165126.113 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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