| RRC ID |
45504
|
| 著者 |
Tamura R, Yoshihara K, Yamawaki K, Suda K, Ishiguro T, Adachi S, Okuda S, Inoue I, Verhaak RG, Enomoto T.
|
| タイトル |
Novel kinase fusion transcripts found in endometrial cancer.
|
| ジャーナル |
Sci Rep
|
| Abstract |
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.
|
| 巻・号 |
5
|
| ページ |
18657
|
| 公開日 |
2015-12-22
|
| DOI |
10.1038/srep18657
|
| PII |
srep18657
|
| PMID |
26689674
|
| PMC |
PMC4687039
|
| MeSH |
Alleles
Amino Acid Sequence
Base Sequence
Cell Line, Tumor
DNA Copy Number Variations / genetics
Endometrial Neoplasms / genetics*
Female
Gene Knockdown Techniques
Humans
Molecular Sequence Data
Oncogene Proteins, Fusion / chemistry
Oncogene Proteins, Fusion / genetics*
Oncogene Proteins, Fusion / metabolism
Protein Kinases / metabolism*
RNA, Messenger / genetics
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Reproducibility of Results
|
| IF |
3.998
|
| 引用数 |
8
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
JHUEM-3(RCB1552) |
