DAXX

Overview

DAXX encodes a multifunctional protein involved in transcriptional regulation, apoptosis, and chromatin remodeling. Together with ATRX, DAXX forms a histone chaperone complex responsible for depositing the histone variant H3.3 at telomeres and pericentromeric heterochromatin. Loss-of-function mutations in DAXX (and ATRX) activate the alternative lengthening of telomeres (ALT) pathway, enabling telomere maintenance independent of telomerase. DAXX mutations are recurrent in pancreatic neuroendocrine tumors and have been identified in treatment-refractory corticotroph pituitary neuroendocrine tumors.

Alterations observed in the corpus

  • Mutations in ATRX/DAXX unique to treatment-refractory corticotroph pituitary neuroendocrine tumors (PitNETs); implicated in activation of the alternative lengthening of telomeres (ALT) pathway; not found in benign/non-refractory PitNETs PMID:38758238.
  • Found recurrently mutated by exome sequencing of pancreatic neuroendocrine tumors (PanNET), with mutations in 25% of tumors PMID:21252315
  • Recurrent loss-of-function in pancreatic and pulmonary neuroendocrine neoplasms (NENs); all DAXX/ATRX-mutant cases fell into transcriptome Cluster A, which showed relative inhibition of MEN1 and DAXX by master-regulator analysis PMID:24326773
  • Mentioned in study PMID:26824661
  • Single-case DAXX mutation detected in PDTC/ATC thyroid cancer targeted sequencing (IMPACT panel, 117 tumors), replicating prior WES ATC study findings PMID:26878173

Cancer types (linked)

  • PTAD: DAXX mutations are exclusive to treatment-refractory corticotroph PitNETs in this cohort; the associated ALT phenotype may contribute to telomere maintenance in aggressive, telomerase-negative tumors; DAXX/ATRX mutations co-occur with other refractory-specific alterations including TERT mutations and TSC2 mutations PMID:38758238.

Co-occurrence and mutual exclusivity

  • DAXX mutations co-occur with ATRX mutations in treatment-refractory corticotroph PitNETs; also observed in the same tumors with TERT mutations (both found exclusively in refractory corticotroph tumors) PMID:38758238.

Therapeutic relevance

  • ALT-positive tumors may have differential sensitivity to agents targeting the ALT pathway or telomere biology (e.g., ATR inhibitors); this rationale has not been tested in PitNETs PMID:38758238.

Open questions

  • Whether DAXX mutation or the ALT phenotype can serve as a biomarker for aggressive PitNET behavior at initial resection (alongside fraction of LOH) requires prospective validation.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:21252315

This page was processed by crosslinker on 2026-05-09. - PMID:24326773

This page was processed by crosslinker on 2026-05-09. - PMID:26824661

This page was processed by wiki-cli on 2026-05-14. - PMID:26878173

This page was processed by entity-page-writer on 2026-05-15.