DDX3X

Overview

DDX3X encodes an X-linked DEAD-box RNA helicase involved in RNA metabolism, translation, and stress granule assembly. DDX3X has roles in regulating apoptosis and innate immune signaling. Somatic mutations in DDX3X have been identified in head and neck squamous cell carcinoma (HNSCC) and classified among apoptosis-related mutations in that context.

Alterations observed in the corpus

  • DDX3X mutated in 4% of HNSCC tumors by whole-exome sequencing of 74 tumor-normal pairs (Broad Institute cohort, hnsc_broad); classified alongside CASP8 as an apoptosis-related significantly mutated gene PMID:21798893
  • Identified as a recurrently mutated gene in pediatric medulloblastoma WGS (PCGP, 37 tumors), with mutations clustered in the helicase domain PMID:22722829
  • DDX3X mutations are recurrent in medulloblastoma across the ICGC WGS/WES cohort of 76 tumors, independently validating its role as a driver enriched in the WNT subgroup PMID:22832583
  • DDX3X is identified as a novel significantly mutated gene in medulloblastoma WES of 92 tumors (Broad cohort), with mutations concentrated in the WNT subgroup and showing male predominance PMID:22820256
  • Identified as significantly mutated in CLL (160 tumors, Broad cohort), with somatic mutations enriched in the RNA helicase domain PMID:23415222
  • Novel candidate SMG (RNA helicase) in cutaneous melanoma; previously unreported in melanoma PMID:26091043
  • Enriched in CLL samples receiving prior therapy; identified as a driver in CLL whole-exome sequencing study of 538 patients (n=278 CLL8 trial) PMID:26466571
  • Subclonal DDX3X variants observed alongside subclonal CTNNB1 hotspot mutations in WNT-subgroup medulloblastomas in the ICGC/CBTTC cohort (n=491), suggesting intratumoral heterogeneity in WNT MB PMID:28726821.

Cancer types (linked)

  • HNSC: DDX3X somatic mutation rate of 4% in whole-exome sequencing cohort (n=74 tumor-normal pairs); identified by MutSig analysis as significantly mutated PMID:21798893

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • No specific therapeutic strategies targeting DDX3X-mutant HNSCC identified in this study. DDX3X is under investigation as a drug target in other cancer types due to its role in translation regulation.

Open questions

  • Specific mutation types (missense, truncating, splice) in HNSCC were not detailed; whether mutations are loss-of-function or gain-of-function is unclear.
  • The mechanism by which DDX3X mutations contribute to HNSCC via apoptosis suppression remains to be functionally validated.

Sources

This page was processed by entity-page-writer on 2026-05-14. - PMID:26466571

This page was processed by wiki-cli on 2026-05-14. - PMID:28726821

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