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#2126 Histone Replacement in Cancer: Dissecting the Role of H3.3 Chaperones in Pancreatic Tumorigenesis

Introduction: Cancer driver mutations affecting the histone H3.3 chromatin remodellers ATRX and DAXX were recently discovered in 43% of sporadic pancreatic neuroendocrine tumours (PNET). Progressive age-dependent replacement of canonical H3.1/2 with H3.3 is crucial for maintaining genome integrity through expression of repressive markers at heterochromatic sites, where loading is mediated by ATRX and DAXX. Loss of H3.3 chaperones in PNET is associated with activation of ALT, a telomere maintenance mechanism, eventually leading to chromosome instability. It has been suggested that ATRX/DAXX expression is necessary for repressing ALT, but mechanistic details of this interaction are not fully understood.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author: Sposito T

Authors: Sposito T, C Nguyen Tu M, Thirlwell C, Salomoni P,

Keywords: PNET, mouse model, epigenetic,