VHL and neoplasm: Meanwhile, DNA methylation studies have shown frequent hyper-methylation in a large fraction of PanNETs and identified several target genes/promoters including RASSF1A, CDKN2A and VHL. Hypo-methylation was also reported for ALU and LINE1, the latter being correlated with poor prognosis and chromosomal instability of ATRX/DAXX-negative tumours (Stefanoli et al. 2014, Di Domenico et al. 2017, Marinoni et al. 2017).