Epigenetic Remodeling upon DAXX and ATRX Loss in Pancreatic Neuro-endocrine tumors (pNETs)

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Introduction: DAXX and or ATRX loss occur in 40% of sporadic pNETs. DAXX and ATRX participate in the cell epigenetic status maintenance. Epigenetic changes influence gene expression, function of telomeres and genomic stability. We hypothesize that DAXX/ATRX loss drives tumor progression in pNET through epigenetic changes affecting genomic stability.

Aim(s): To investigate the epigenetic changes occurring upon DAXX and ATRX loss.

Materials and methods: LINE1 and global DNA methylation levels were assessed respectively in 24 and 105 human pNETs by pyrosequencing and IHC (Immuno Histo Chemistry) and correlated with DAXX/ATRX status, ALT (Alternative Lengthening Telomeres) activation and CIN (Chromosomal Instability). H3K4me3 levels were evaluated by IHC in 105 pNET samples. DNA methylation status as well as H3K4me3 and CIN were measured in vitro upon DAXX knock-down in pNET cell lines.

Conference: 13th Annual ENETSConcerence (2016)

Presenting Author:

Authors: Marinoni I, Wiederkeher A, Pantasis S, Normand L, Wiedmer T,

Keywords: DAXX/ATRX, epigenetic, CIN,