Montal, RobertAndreu Oller, CarmenBassaganyas, LaiaEsteban Fabró, RogerMoran, SebastianMontironi, CarlaMoeini, AgrinPinyol, RoserPeix, JuditCabellos, LaiaVillanueva, AugustoSia, DanielaMazzaferro, VincenzoEsteller, Manel, 1968-Llovet i Bayer, Josep Maria2020-01-082020-01-082019-07-09https://hdl.handle.net/2445/147217The clinical utility of serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC) is widely recognised. However, a clear understanding of the mechanisms of AFP overexpression and the molecular traits of patients with AFP-high tumours are not known. We assessed transcriptome data, whole-exome sequencing data and DNA methylome profiling of 520 HCC patients from two independent cohorts to identify distinct molecular traits of patients with AFP-high tumours (serum concentration?>?400?ng/ml), which represents an accepted prognostic cut-off and a predictor of response to ramucirumab. Those AFP-high tumours (18% of resected cases) were characterised by significantly lower AFP promoter methylation (p?<?0.001), significant enrichment of progenitor-cell features (CK19, EPCAM), higher incidence of BAP1 oncogene mutations (8.5% vs 1.6%) and lower mutational rates of CTNNB1 (14% vs 30%). Specifically, AFP-high tumours displayed significant activation of VEGF signalling (p?<?0.001), which might provide the rationale for the reported benefit of ramucirumab in this subgroup of patients.3 p.application/pdfeng(c) Montal et al., 2019Càncer de fetgeOncogènesiLiver cancerCarcinogenesisinfo:eu-repo/semantics/article6953882020-01-08info:eu-repo/semantics/openAccess570624931285588