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Fig. 6 | Genome Biology

Fig. 6

From: PiggyBac mutagenesis and exome sequencing identify genetic driver landscapes and potential therapeutic targets of EGFR-mutant gliomas

Fig. 6

Effects of PB insertions on glioma transcriptomes. a RNA-seq was performed on tumors from EGFRvIII-PB mice (n = 36), with IM-Fusion [80] analysis of the data to identify fusion transcripts. b Overview of the effect ATP1-S2 transposons on the transcriptome: the transposon can insert in the sense orientation upstream of a gene’s promoter or in an early intron, driving gene transcription through the transposon’s promoter and splice donor (SD). Alternatively, it can cause transcript termination by inserting in an intron in either sense or antisense orientation because of its two splice acceptors (SA1 = CbASA; SA2 = En2SA) and bi-directional polyA sites; transcript termination can have the effect of inactivating tumor suppressor genes, but also potentially activating an oncogene if there are downstream inhibitory domains for the protein that are removed. c Of all genes with fusion transcripts, 80 genes overlapped with CIS genes identified by QI-seq. P value was calculated using a two-sided Fisher’s exact test. All fusion transcripts detected with the carp-beta-actin splice acceptor (CbASA) and splice donor (SD) contained piggyBac in the sense orientation, and all those with Engrailed-2 exon-2 splice acceptor (En2SA) contained piggyBac in the antisense orientation, suggesting the transposon insertion had functional consequences in all cases. d Bar plot showing percentage of gliomas with fusion transcripts among top 20 CIS genes (Qki is also included here). e Top fusion transcripts containing the PB splice donor ranked by read count; among them, only Rad51b was also identified as a CIS gene

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