論文

国際誌
2015年12月22日

Novel kinase fusion transcripts found in endometrial cancer.

Scientific reports
  • Ryo Tamura
  • ,
  • Kosuke Yoshihara
  • ,
  • Kaoru Yamawaki
  • ,
  • Kazuaki Suda
  • ,
  • Tatsuya Ishiguro
  • ,
  • Sosuke Adachi
  • ,
  • Shujiro Okuda
  • ,
  • Ituro Inoue
  • ,
  • Roel G W Verhaak
  • ,
  • Takayuki Enomoto

5
開始ページ
18657
終了ページ
18657
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/srep18657

Recent advances in RNA-sequencing technology have enabled the discovery of gene fusion transcripts in the transcriptome of cancer cells. However, it remains difficult to differentiate the therapeutically targetable fusions from passenger events. We have analyzed RNA-sequencing data and DNA copy number data from 25 endometrial cancer cell lines to identify potential therapeutically targetable fusion transcripts, and have identified 124 high-confidence fusion transcripts, of which 69% are associated with gene amplifications. As targetable fusion candidates, we focused on three in-frame kinase fusion transcripts that retain a kinase domain (CPQ-PRKDC, CAPZA2-MET, and VGLL4-PRKG1). We detected only CPQ-PRKDC fusion transcript in three of 122 primary endometrial cancer tissues. Cell proliferation of the fusion-positive cell line was inhibited by knocking down the expression of wild-type PRKDC but not by blocking the CPQ-PRKDC fusion transcript expression. Quantitative real-time RT-PCR demonstrated that the expression of the CPQ-PRKDC fusion transcript was significantly lower than that of wild-type PRKDC, corresponding to a low transcript allele fraction of this fusion, based on RNA-sequencing read counts. In endometrial cancers, the CPQ-PRKDC fusion transcript may be a passenger aberration related to gene amplification. Our findings suggest that transcript allele fraction is a useful predictor to find bona-fide therapeutic-targetable fusion transcripts.

リンク情報
DOI
https://doi.org/10.1038/srep18657
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26689674
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687039
ID情報
  • DOI : 10.1038/srep18657
  • PubMed ID : 26689674
  • PubMed Central 記事ID : PMC4687039

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