EML4

Overview

EML4 (echinoderm microtubule-associated protein-like 4) is best known as the most common fusion partner of ALK in non-small cell lung cancer. The EML4::ALK fusion is a canonical oncogenic driver and a primary target of ALK inhibitors.

Alterations observed in the corpus

  • EML4::ALK fusions were detected in CSF ctDNA from lung carcinoma patients with CNS involvement, profiled by MSK-IMPACT in the csf_msk_2024 cohort (1,007 CSF samples, 711 patients). ALK resistance mutations (p.G1202R, p.G1269A) were detected upon targeted therapy progression in EML4::ALK-positive patients PMID:39289779.
  • EML4-ALK translocation status (FISH) was annotated for 196/211 resected early-stage NSCLC patients in the Stanford NSCLC-Radiogenomics cohort as part of a paired radiogenomic dataset; per-subject status is provided as a data record rather than aggregate frequencies PMID:30325352.
  • Mentioned in the context of RTK-targeted therapy landscape in HCC (2014 genomics review) PMID:24735922
  • EML4/ALK fusion detected in papillary thyroid carcinoma (PTC); part of 4/484 (0.8%) ALK fusions in the TCGA PTC cohort; represents a potentially targetable alteration. PMID:25417114
  • EML4 is a fusion partner for ALK in PDTC (poorly differentiated thyroid cancer); ALK-EML4 fusions are present in 14% of PDTCs overall (together with other ALK partners STRN and novel CCDC149), mutually exclusive with BRAF/RAS mutations, and enriched in younger patients (median 49 vs 58 years) PMID:26878173
  • EML4-ALK fusion is the predominant ALK rearrangement in young lung cancer (>80% of ALK+ cases per Tian et al.); ALK rearrangements are over-represented in YLC vs older NSCLC and are targetable with crizotinib and lorlatinib PMID:27346245
  • EML4–NTRK3 fusion detected in congenital fibrosarcoma (IFS) in the PIPseq pediatric cohort; RNA-seq was required to detect the fusion and supported diagnostic reclassification from undifferentiated sarcoma to infantile fibrosarcoma; flagged as an ALK-inhibitor target PMID:28007021.
  • EML4-ALK fusion detected in n=38 cases, predominantly LUAD, within the MSK-IMPACT pan-cancer cohort of 10,336 patients PMID:28481359
  • EML4-ALK is one of the ALK fusions detected across 20 samples spanning 8 cancer types (5 in LUAD) in the TCGA pan-cancer fusion landscape; EML4 is the most frequent 5’ partner (7/17 ALK-fusion samples); fusion status corresponds to copy-number-neutral ALK overexpression, forming the rationale for crizotinib and other approved ALK inhibitors PMID:29617662.

Cancer types (linked)

  • NSCLC — EML4::ALK fusions detected in CSF ctDNA from lung carcinoma patients with CNS tumors PMID:39289779.

Co-occurrence and mutual exclusivity

  • Not reported in the corpus.

Therapeutic relevance

  • EML4::ALK fusions are level 1 OncoKB actionable alterations in NSCLC, targetable by ALK inhibitors; serial CSF ctDNA profiling identified emergence of ALK resistance mutations in EML4::ALK-positive patients PMID:39289779.

Open questions

  • None flagged in the corpus.

Sources

This page was processed by crosslinker on 2026-05-14. - PMID:24735922

This page was processed by crosslinker on 2026-05-14. - PMID:25417114

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

This page was processed by entity-page-writer on 2026-05-15. - PMID:27346245

This page was processed by entity-page-writer on 2026-05-15. - PMID:28007021

This page was processed by wiki-cli on 2026-05-14. - PMID:28481359

This page was processed by wiki-cli on 2026-05-15. - PMID:29617662

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