Ultra-Deep Targeted Resequencing Reveals Recurrent DAXX and CYFIP2 Mutations and Implicates Novel Pathways in Pancreatic Neuroendocrine Tumors

#2283

Introduction: Recent studies in pancreatic neuroendocrine tumors have identified mutations in DAXX/ATRX, MEN1, and genes involved in the phosphoinositide-3-kinase/Akt/mammalian target of rapamycin (PI3K-Akt-mTOR) pathway. However, these studies focused on abundant mutations.

Aim(s): Ultra-deep sequencing of formalin-fixed paraffin-embedded matched tumor-normal tissue of 38 patients using a Haloplex targeted resequencing panel, consisting of 20 genes.

Materials and methods: Combined VarScan2 and novel amplicon-based single nucleotide calling algorithms were used to identify both SNVs present >10% of reads (high-abundance) and in <10% of reads (low-abundance). Impact on protein function was evaluated using multiple dbSNFP v3.0 impact prediction algorithms. Found variants were validated by Sanger sequencing.

Conference: 15th Annual ENETSConcerence (2018)

Presenting Author: Vandamme T

Authors: Vandamme T, Beyens M, Van Camp G, Boons G, Hofland L,

Keywords: pancreatic neuroendocrine tumors, PNET, genetics, tumor heterogeneity, hotspot mutations,