DAXX and ATRX Loss Defines Chromosomal Instability and Poor Outcome in Pancreatic NET Abstract #856

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 ENETS Conference 2014 (2014)
Category: ...none of the below
Presenting Author: PhD Ilaria Marinoni
Keywords: pNET, Daxx, Atrx, ALT, CIN

To read results and conclusion, please login ...

Further abstracts you may be interested in

#1312 Epigenetic Remodeling upon DAXX and ATRX Loss in Pancreatic Neuro-endocrine tumors (pNETs)
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.
Conference: 13th Annual ENETS conference 2016 (2016)
Category: Basic Science - Genetics, epigenetics, miRNAs
Presenting Author: Ilaria Marinoni
Keywords: DAXX/ATRX, epigenetic, CIN
#2986 Characterization of 142 Human Pancreatic Neuroendocrine Tumors: ATRX and DAXX Correlation with Clinical-Pathological Data
Introduction: Pancreatic neuroendocrine tumors (PNETs) are rare and heterogeneous neoplasms with a 10-year survival rate less than 30%. Up to 43% of them are driven by inactivating mutations in ATRX or DAXX. These are important players at chromatin remodeling, that when mutated prone cancer cells to initiate the alternative lengthening of telomeres (ALT). ALT phenotype correlates with in situ loss of expression of the proteins ATRX or DAXX and can be corroborated by telomere-FISH.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Basic Science - Signaling pathways, receptors, biomarkers
Presenting Author: DVM Tiago B Gaspar
#2795 Molecular Correlation of the Activity of Evofosfamide (EVO) in Combination with Sunitinib (SUN) in Pancreatic Neuroendocrine Tumors (pNETs) in the SUNEVO GETNE Trial
Introduction: MEN1, DAXX, ATRX, and PI3K/AKT/mTOR pathway genes are frequently mutated in pNETs. Sunitinib is approved and widely used in the metastatic setting but unfortunately, no validated predictive biomarker has been identified to guide therapy yet. The SUNEVO phase II trial of the Spanish Task Force Group for Neuroendocrine and Endocrine Tumours (GETNE) trial combined the pro-drug of EVO under SUN-induced hypoxic conditions.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Trials in Progress/Trials in Concept
Presenting Author: Dr. Enrique Grande
#3007 An mRNA-based Classifier Identifies PanNETs with Different Clinicopathological Characteristics
Introduction: Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms that varies from indolent to highly aggressive diseases. Previous studies have suggested alterations of ATRX/DAXX as biomarkers of dismal prognosis, yet inconclusive data (especially in the metastatic setting) prevent those biomarkers to be used as routine clinical tests.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Basic Science - Genetics, epigenetics, miRNAs, Omics
Presenting Author: Dr Caterina Vicentini
#2902 DNA Methylation Analysis of the PDX1 Gene Can Be Used for PNET Subtyping and Has a Possible Prognostic Value
Introduction: Estimating prognosis of pancreatic neuroendocrine tumor (PNET) patients remains challenging. Mutation status of DAXX/ATRX/MEN1, histone modification patterns and immunohistochemistry for relevant transcription factors, including PDX1, were recently used to perform subtyping and distinguished two main types, A and B. These subtypes are linked to cell-of-origin and associated with clinical outcome.
Conference: 17th Annual ENETS Conference 2020 (2020)
Category: Basic Science - Genetics, epigenetics, miRNAs, Omics
Presenting Author: Gitta Boons