DAXX and ATRX Loss Defines Chromosomal Instability and Poor Outcome in Pancreatic NET

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Introduction: Chromosomal Instability (CIN) has been reported in pancreatic neuroendocrine tumors (pNETs) with poor outcome. However, no specific genetic background has been associated with CIN. Whole exome sequencing revealed mutations in DAXX (Death domain associated protein gene) and ATRX (ATR-X gene) in 40% of pNETs. DAXX and ATRX mutations in pNETs are associated with Alternative Lengthening of Telomeres (ALT) activation.

Aim(s): To assess whether DAXX/ATRX loss and consequent ALT activation is related to CIN in pNETs and if DAXX/ATRX loss defines a clinically relevant molecular subtype.

Materials and methods: We performed DAXX and ATRX IHC and Telomeric FISH on two different pNET collectives comprising a total of 243 well-differentiated primary pNET. Of these, follow-up data was available for 149 patients. We correlated loss of DAXX/ATRX expression and ALT activation with CGH (Comparative Genomic Hybridization) array data, as well as with clinicopathological characteristics, tumor relapse and survival data.

Conference: 11th Annual ENETSConcerence (2014)

Presenting Author:

Authors: Marinoni I, Schmitt A, Vassella E, Dettmer M, Rudolph T,

Keywords: pNET, Daxx, Atrx, ALT, CIN,