ERBB4

Overview

ERBB4 (HER4) is a receptor tyrosine kinase of the ErbB/HER family. It has been identified as a target of somatic mutation in soft tissue sarcomas, including pleomorphic liposarcoma and myxofibrosarcoma, though the functional significance of individual mutations identified by targeted resequencing remains to be established.

Alterations observed in the corpus

  • Somatic mutations found upon targeted resequencing of 722 protein-coding and microRNA genes in pleomorphic liposarcoma (PLLS) and myxofibrosarcoma (MFS) samples across 207 high-grade soft tissue sarcomas (sarc_mskcc); functional impact of individual mutations was not established and “further studies will be needed” PMID:20601955.
  • 9 mutations in 188 LUAD tumours; 2 in kinase domain, 5 in receptor ligand binding domain; recurrently mutated receptor tyrosine kinase. PMID:18948947
  • ERBB4 K901N detected at resistance to KRASG12C + EGFR inhibition in CRC patient ctDNA PMID:36355783
  • Somatic mutations identified in medulloblastoma WGS/WES cohort (ICGC, 76 tumors) PMID:22832583
  • ERBB4 recurrently affected by structural variants (SV) in rhabdomyosarcoma (RMS) genomic characterization; part of the 93%-targetable kinase signaling axis PMID:24436047
  • Activating mutations in RTK signaling identified in ESCC (139 paired tumor/germline samples by whole-exome/targeted sequencing) PMID:24686850
  • ERBB-pathway member cited in context of prior GBC whole-exome data showing recurrent ERBB-pathway mutations activating AKT in GBC PMID:24997986
  • Mutated in 20/294 GC cases (~6.8%); kinase-domain (33%) and receptor-domain (20%) mutations; p.R50C shared with melanoma hotspot. With NRG1, defines a candidate lapatinib-targetable subset (~11.6% of GCs carry NRG1 and/or ERBB4 mutations). PMID:25583476
  • E563K activating mutation in cSCC; this allele previously reported in 19% of melanomas PMID:25589618
  • More frequently mutated in HR+/HER2− metastatic breast cancer (BRCA) vs early breast cancer at FDR<0.1; 9 missense mutations in 8 mBCs including hotspots COSM4764538 and COSM1015992; 5/8 were HR+/HER2−; functional consequences require experimental validation PMID:28027327.
  • ERBB4 (HER4) mutations were catalogued across cancer types in a large-scale targeted sequencing study PMID:28336552
  • ERBB4 is a KIRC SMG uniquely called by MuSiC2 (after long-gene filtering) in the TCGA MC3 MAF pan-cancer analysis; it was not recovered by MutSig2CV, illustrating caller-specific sensitivity differences in the multi-tool somatic variant calling framework PMID:29596782.

Cancer types (linked)

Co-occurrence and mutual exclusivity

  • No co-occurrence or mutual exclusivity patterns reported in the corpus to date.

Therapeutic relevance

  • No direct therapeutic data in the corpus. ERBB4 is a known driver in some carcinomas (e.g., breast, lung) but its therapeutic relevance in sarcoma subtypes remains unestablished.

Open questions

  • Whether ERBB4 mutations in PLLS/MFS are driver events or passenger mutations is unresolved; functional validation is absent in the current study PMID:20601955.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:18948947

This page was processed by crosslinker on 2026-05-14. - PMID:36355783

This page was processed by crosslinker on 2026-05-14. - PMID:22832583

This page was processed by crosslinker on 2026-05-14. - PMID:24436047

This page was processed by crosslinker on 2026-05-14. - PMID:24686850

This page was processed by crosslinker on 2026-05-14. - PMID:24997986

This page was processed by crosslinker on 2026-05-14. - PMID:25583476

This page was processed by crosslinker on 2026-05-14. - PMID:25589618

This page was processed by crosslinker on 2026-05-14. - PMID:28027327

This page was processed by wiki-cli on 2026-05-14. - PMID:28336552

This page was processed by wiki-cli on 2026-05-14. - PMID:29596782

This page was processed by wiki-cli on 2026-05-15.