Identification of fusion genes in XXXX by paired-end RNA-sequencing.

@entity20871 @entity0 @entity5 @entity38839 @entity72271 @entity1778 @entity34408
BACKGROUND: Until recently, chromosomal translocations and fusion genes have been an underappreciated class of mutations in solid @entity5 . Next-generation sequencing technologies provide an opportunity for systematic characterization of @entity5 cell transcriptomes, including the discovery of expressed fusion genes resulting from underlying genomic rearrangements. RESULTS: We applied paired-end RNA-seq to identify 24 novel and 3 previously known fusion genes in @entity0 cells. Supported by an improved bioinformatic approach, we had a 95% success rate of validating gene fusions initially detected by RNA-seq. Fusion partner genes were found to contribute promoters (5' UTR), coding sequences and 3' UTRs. Most fusion genes were associated with copy number transitions and were particularly common in high-level DNA amplifications. This suggests that fusion events may contribute to the selective advantage provided by DNA amplifications and deletions. Some of the fusion partner genes, such as @entity20871 in the @entity72271 - @entity20871 fusion and @entity38839 in the @entity34408 - @entity38839 fusion, were only detected as a fusion transcript, indicating activation of a dormant gene by the fusion event. A number of fusion gene partners have either been previously observed in oncogenic gene fusions, mostly in @entity1778 , or otherwise reported to be oncogenic. RNA interference-mediated knock-down of the @entity34408 - @entity38839 fusion gene indicated that it may be necessary for @entity5 cell growth and survival. CONCLUSIONS: In summary, using RNA-sequencing and improved bioinformatic stratification, we have discovered a number of novel fusion genes in @entity0 , and identified @entity34408 - @entity38839 as a potential fusion gene with importance for the growth and survival of @entity0 cells.
