ALK G1202R resistance mutation
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BIO-ALK-G1202R |
|---|---|
| Type | Biomarker |
| Aliases | ALK G1202R — мутація резистентностіALK p.G1202RALK solvent-front mutation |
| Status | reviewed 2026-04-27 | pending_clinical_signoff |
| Diseases | None declared |
| Sources | SRC-CROWN-SOLOMON-2021 SRC-ESMO-NSCLC-METASTATIC-2024 SRC-NCCN-NSCLC-2025 |
Biomarker Facts
| Biomarker type | gene_mutation |
|---|---|
| Mutation details | {"exon": "23", "functional_impact": "pan-ALK-TKI resistance (crizotinib, ceritinib, alectinib, brigatinib); retains sensitivity to lorlatinib", "gene": "ALK", "hgvs_protein": "p.G1202R", "variant_type": "missense"} |
| Measurement | MethodctDNA NGS (preferred at TKI progression) OR repeat tumor biopsy NGS; targeted ALK-resistance panels acceptable Unitscategorical (positive | negative); VAF % when reported Sensitivity requirementVAF ≥0.5% (cfDNA) given typically sub-clonal emergence |
| Actionability lookup | {"gene": "ALK", "variant": "G1202R"} |
| Related biomarkers | BIO-ALK-FUSION BIO-ALK-REARRANGEMENT BIO-ALK-L1196M |
Notes
Most common on-target ALK-resistance mutation after 2nd-generation TKI (alectinib, brigatinib): emerges in ~20-40% of post-2G-TKI re-biopsies. Solvent-front position blocks binding of 1st/2nd-gen ALK inhibitors. Lorlatinib (3rd-gen, macrocyclic) maintains activity per CROWN trial data and post-progression analyses; preferred 2L+ option when G1202R detected. Compound mutations (G1202R + L1196M, G1202R + I1171N, etc.) may emerge under lorlatinib pressure and confer pan-ALK-TKI resistance — trial enrollment indicated.
Used By
Biomarker
BIO-ALK-L1196M- ALK L1196M gatekeeper resistance mutation
Red flag
RF-IMT-TRANSFORMATION-PROGRESSION- IMT progression on first-line crizotinib (acquired ALK kinase-domain resistance mutation...