Clonally selected SB insertion events affect trunk driver gene expression in SB-induced cuSCC genomes.

Seven cuSCC genomes with mutually exclusive high-read depth Zmiz1 or Zmiz2 SB insertions were selected for RNA-seq analysis of SB-fusion transcripts and global gene expression levels. (A) Genes with the most abundant SBfusion reads detected by wtRNA-seq analysis of the 7 cuSCC tumors. (B) Predicted gene expression effects of SB insertions in 10 drivers with high read-depth SB insertions. (C) High positive correlation between SBCapSeq read depth and Zmiz1 expression by wtRNA-seq analysis. (D) Multifold induction of gene expression in cuSCC masses with (+) high read depth activating SB insertion events among 4 candidate oncogenic drivers compared with normal gene expression levels in cuSCC tumors without (–) SB insertions. Individual gene plots may be found in (S14 and S15 Tables). (E) Reduced gene expression in cuSCC masses with (+) high read depth inactivating SB insertion events among 6 candidate tumor suppressor drivers compared with normal gene expression levels in cuSCC tumors without (–) SB insertions. Individual gene plots may be found in (S14 and S15 Tables).