RET alterations (fusion or activating point mutation)
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-RET |
|---|---|
| Type | Biomarker |
| Aliases | RET C634RRET M918TRET alterationsRET fusionRET-rearrangedАльтерації RET (фузія або активуюча точкова мутація) |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 SRC-ONCOKB |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"functional_impact": "Constitutive RET tyrosine kinase activation", "gene": "RET", "gene_hugo_id": "HGNC:9967", "hotspots": ["KIF5B-RET fusion (most common in NSCLC)", "CCDC6-RET fusion (PTC)", "NCOA4-RET fusion (PTC)", "M918T (germline MEN2B; somatic in sporadic MTC)", "C634R / C634F / C634Y (germline MEN2A — codon 634 cysteine)", "C611 / C618 / C620 / C630 cysteine substitutions (MEN2A spectrum)"], "variant_type": "fusion / missense"} |
| Measurement | MethodRNA-NGS (preferred for fusion sensitivity) + DNA-NGS (point mutations) OR FISH break-apart (fusion screen) OR allele-specific PCR (codon 634 / M918T) Unitscategorical (positive/negative); fusion partner reported Sensitivity requirementRNA-NGS captures fusion partners; germline testing required for any MTC patient at presentation |
| Related biomarkers | None declared |
Notes
Fusions: ~1–2% of NSCLC adenocarcinoma; ~10–20% of papillary thyroid carcinoma. Selpercatinib (LIBRETTO-001 / -431) and pralsetinib (ARROW) are approved for RET-fusion+ NSCLC and PTC. Point mutations (M918T, codon 634): hereditary medullary thyroid carcinoma in MEN2A (C634) / MEN2B (M918T) and ~50% of sporadic MTC. Selpercatinib and pralsetinib are 1L for advanced RET-mutant MTC (LIBRETTO-001, ARROW); multikinase TKIs (vandetanib, cabozantinib) are alternatives. Germline testing is mandatory for any MTC patient.
Used By
Actionability
BMA-RET-C634R-MTC- RET C634R is the most common MEN2A germline variant. In advanced / metastatic MEN2A-drive...BMA-RET-CCDC6-NSCLC- CCDC6-RET fusion is the second-most common RET fusion in NSCLC (~10-20%). Response to sel...BMA-RET-FUSION-NSCLC- RET fusion in advanced NSCLC (~1-2% of adenocarcinoma): selpercatinib (LIBRETTO-001 Drilo...BMA-RET-FUSION-THYROID-PAPILLARY- RET fusion in papillary thyroid carcinoma (PTC) — ~5-10% sporadic, enriched in radiation-...BMA-RET-KIF5B-NSCLC- KIF5B-RET is the most common RET fusion in NSCLC (~70% of RET+ NSCLC). Treatment is ident...BMA-RET-M918T-MTC- RET M918T in medullary thyroid carcinoma (MTC): selpercatinib superior to cabozantinib/va...
Algorithms
ALGO-MTC-1L- ALGO-MTC-1L
Biomarker
BIO-RET-M918T- RET M918T mutation (MEN2B / sporadic MTC)
Diseases
DIS-MTC- Medullary thyroid carcinoma (MTC)DIS-THYROID-ANAPLASTIC- Anaplastic thyroid carcinoma (ATC)DIS-THYROID-PAPILLARY- Papillary thyroid carcinoma (PTC)
Indications
IND-MTC-ADVANCED-1L-CABOZANTINIB-RET-WT- IND-MTC-ADVANCED-1L-CABOZANTINIB-RET-WTIND-MTC-ADVANCED-1L-SELPERCATINIB- IND-MTC-ADVANCED-1L-SELPERCATINIBIND-NSCLC-2L-PD-L1-POST-IO-DOCETAXEL- IND-NSCLC-2L-PD-L1-POST-IO-DOCETAXELIND-NSCLC-2L-RET-FUSION-SELPERCATINIB- IND-NSCLC-2L-RET-FUSION-SELPERCATINIB
Questionnaires
QUEST-MTC-1L-STUB- Medullary thyroid carcinoma — first lineQUEST-NSCLC-1L-STUB- Non-small cell lung cancer — first line
Red flag
RF-IMT-HIGH-RISK-BIOLOGY- Inflammatory myofibroblastic tumor with actionable fusion driver: ALK fusion (TPM3-ALK, T...RF-MTC-HIGH-RISK-BIOLOGY- Medullary thyroid carcinoma with actionable RET mutation: germline RET M918T (MEN2B — mos...RF-MTC-RET-MUTANT- RET proto-oncogene activating mutation (somatic or germline) in advanced or metastatic me...RF-THYROID-ANAPLASTIC-HIGH-RISK-BIOLOGY- Anaplastic thyroid carcinoma with actionable driver mutation: BRAF V600E (~25-40% ATC; da...RF-THYROID-PAPILLARY-HIGH-RISK-BIOLOGY- Papillary thyroid carcinoma with adverse molecular / clinical features: BRAF V600E (~60%...