ArticleClinical & experimental metastasis2026
NF1 mutation may be associated with lung-tropic metastasis in cutaneous melanoma: a genomic analysis of 520 patients.
Article in Clinical & experimental metastasis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMetastatic organotropism in cutaneous melanoma remains incompletely understood at the genomic level. While prior work has linked BRAF and NRAS mutations to organ-specific metastasis patterns, the role of NF1 has not been systematically evaluated. We investigated whether NF1 mutation is specifically associated with lung metastasis in cutaneous melanoma.
methodsWe analyzed 520 patients with metastatic cutaneous melanoma from the MSK-MET cohort, comparing 258 with documented lung metastasis to 262 without. Gene-level enrichment was tested across 118 genes meeting a 5% mutation-frequency threshold on the shared MSK-IMPACT panel, with Benjamini-Hochberg false discovery correction. Robustness was evaluated by panel-stratified, era-stratified, Cochran-Mantel-Haenszel, and bias-corrected bootstrap analyses. Organ specificity was tested across 12 metastatic sites. Multivariable logistic regression adjusted for tumor mutational burden (TMB), age, and sequencing panel. Overall survival was analyzed by Cox proportional hazards modeling.
resultsNF1 was the single gene crossing the primary significance threshold (OR 2.11, 95% CI 1.40-3.21; p = 1.89 × 10
conclusionsNF1 mutation is the strongest gene-level correlate of lung-selective metastasis in cutaneous melanoma. The NF1-mutant subtype may represent a dual-biomarker population and could warrant both pulmonary surveillance and prospective evaluation for immunotherapy.
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