RET

Overview

RET encodes a receptor tyrosine kinase involved in cell growth, differentiation, and survival. It is cataloged among the genes targeted by multi-kinase inhibitors under investigation in nasopharyngeal carcinoma (NPC).

Alterations observed in the corpus

  • RET is listed among genes targeted by multi-kinase inhibitors under investigation in recurrent/metastatic NPC. PMID:24952746
  • Fusions in 2/230 (0.9%) LUAD cases (TCGA); exclusively in the transversion-low (TL) non-smoker subset (P = 1.85×10⁻⁴ for fusion enrichment in TL). PMID:25079552
  • RET fusions in 6.8% (33/484) of PTCs; most fusions weakly BVL (BRAFV600E-like expression score); 4 novel kinase-domain-preserving RET fusion partners discovered; mutually exclusive with BRAF/RAS/EIF1AX point mutations (Fisher’s exact p=4.9×10⁻⁴³). PMID:25417114
  • RET found fused with CCDC6 or NCOA4 in 5 PDTCs in a targeted-sequencing study of advanced thyroid cancers; RET fusions were restricted to PDTC (not ATC) in this cohort. PMID:26878173
  • RET rearrangements occur in ~9.5% of young lung cancer patients (YLC, age ≤45) versus ~1% in patients >45 years per cBioPortal analysis; ERC1-RET fusion observed in Indian cohort PMID:27346245.
  • Germline C634 (extracellular) vs somatic M918 (intracellular tyrosine kinase) mutations differentiate hereditary from sporadic PCC/PGL (p < 0.001); RET-mutant tumors overexpress RET (p < 0.003) in a comprehensive multi-omic PCC/PGL study PMID:28162975
  • Fusions in 1.7–3.8% of LUAD patients; level 2A actionability; 53.3% received matched therapy with 72.7% clinical benefit rate; cabozantinib cited as matched agent PMID:28336552
  • Kinase fusions enriched in LUAD but also detected across 11 additional tumor types in 10,336 MSK-IMPACT cases PMID:28481359
  • One NCOA4-RET fusion observed in MSS mCRC in a 1,640-tumor targeted sequencing cohort PMID:29316426
  • Reported at 1% frequency as an actionable driver in NSCLC with too few events for response analysis in the MSK-IMPACT anti-PD-(L)1 TMB cohort (n=240) PMID:29337640
  • CCDC6–RET and other RET fusions are recurrent in THCA (4.2%; 33 samples flagged as druggable) and also seen in LUAD; RET is among the top 3’-kinase recurrent partners in the TCGA 9,624-sample pan-cancer fusion catalog, with intact kinase domains and elevated 3’ expression consistent with promoter-swap-driven oncogene activation PMID:29617662.

Cancer types (linked)

  • NPC — RET is a component of the multi-kinase inhibitor target profile (alongside VEGFR2/KDR, FLT3, TEK, and others) in R/M NPC. PMID:24952746

Co-occurrence and mutual exclusivity

  • No co-occurrence or mutual exclusivity data reported in the current corpus.

Therapeutic relevance

  • Multi-kinase TKIs active against RET are being investigated in NPC primarily as anti-angiogenic/anti-proliferative agents rather than RET-alteration-selected strategies. PMID:24952746

Open questions

  • RET-specific mutation frequency in NPC and whether RET alterations are predictive of TKI response are uncharacterized in the current corpus.

Sources

This page was processed by entity-page-writer on 2026-05-15. - PMID:29316426

This page was processed by wiki-cli on 2026-05-15. - PMID:29337640

This page was processed by entity-page-writer on 2026-05-15. - PMID:29617662

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