Fig. 1
Diverse mechanisms leading to CCNA2 activation in HCC. a Summary of structural rearrangements (top) and viral insertions (bottom) affecting CCNA2 gene identified in 751 HCC from the LICA-FR, TCGA and ICGC-JP cohorts. b Sorted CCNA2 expression (log scale) in the LICA-FR and TCGA cohorts. Gene expression was obtained from RNA-seq data and is given in fragments per kilobase of exons per million reads (FPKM). Samples harboring structural variants (SV) or viral insertions are indicated with a color code. c Functional consequences of AAV2 and HBV insertions in CCNA2. Viral insertions identified in the LICA-FR cohort were precisely mapped using WGS or viral capture data, and RNA-seq reads were aligned on the reconstructed chimeric DNA to identify the transcription start sites and predicted translation initiation sites of abnormal transcripts. d CCNA2 fusions identified in the LICA-FR, TCGA and ICGC-JP cohorts. The transcription start site of the fusion transcript is represented together with the predicted translation initiation site. Fusions with KIAA1109, LIPC and TDO2 involve 5′ exons not annotated in transcript databases but expressed in normal liver. e Schematic representation of cyclin A2 protein with functional domains. D-box Destruction box; Ub, Ubiquitination targeting sequences. f Western blot analysis of cyclin A2 using antibodies targeting the N-terminal (top) or C-terminal (middle) domains. Tumors with viral insertions or gene fusions are compared with tumors without CCNA2 alteration and non-tumoral liver controls
