TLR4

Overview

TLR4 (Toll-like receptor 4) is a pattern-recognition receptor central to innate immune signaling. In esophageal adenocarcinoma (EAC), TLR4 is recurrently mutated with mutations clustering in the MD-2 interaction region, suggesting a functional impact on TLR4-MD-2 complex formation and downstream innate immune signaling. Its recurrent mutation in EAC implicates immune evasion or inflammatory signaling dysregulation as a contributor to EAC pathogenesis.

Alterations observed in the corpus

  • Mutated in 6% of EAC tumors (145-tumor WES cohort); mutations cluster in the MD-2 interaction region (p.D379–p.F487), including the recurrent p.E439 variant; nominated as a statistically significant candidate driver PMID:23525077.

Cancer types (linked)

  • EAC: Recurrent missense mutations in the MD-2 interaction domain; 6% prevalence in a 145-tumor whole-exome sequencing cohort PMID:23525077.

Co-occurrence and mutual exclusivity

  • No co-occurrence or mutual exclusivity patterns reported for TLR4 specifically in this cohort PMID:23525077.

Therapeutic relevance

  • No therapeutic agents targeting TLR4 were evaluated in this study; functional impact on innate immune signaling in EAC awaits experimental validation PMID:23525077.

Open questions

  • Functional consequences of TLR4 mutations in the MD-2 interaction region in EAC have not been experimentally validated; the impact on TLR4-ligand recognition and downstream NF-kB signaling is unknown PMID:23525077.

Sources

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