ArticleBritish journal of cancer2026
Genetic landscape of stage II melanoma identifies CBL as a new driver gene and prognostic biomarker.
Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- CBL in stage II melanoma: considerations of variant interpretation for driver gene designation.British journal of cancer · 2026Article
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16 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundWhile adjuvant therapies are currently recommended for patients with stage IIB-IV melanoma, biomarkers are missing to improve risk stratification to select the most efficient treatment and patients to be included in clinical trials. We genetically characterized a large cohort of patients with stage-II-melanoma to identify predictive and prognostic biomarkers.
methodsClinical data of 193 stage-II-melanoma patients from the German Central Malignant Melanoma Registry were identified. All patients were therapy-naïve at the time of primary resection and received no adjuvant treatment until recurrence. Tumour-normal pairs were sequenced with a comprehensive cancer panel.
results30.1% of the tumours were classified as BRAF-mutated, 28.0% as RAS-, 18.1% as NF1-, and 23.8% as Triple-WT. In-silico prediction identified a potential new candidate driver, CBL, in 10.4% of the patients. GISTIC nominated deletions of region 11q23.1-3 containing CBL as a potential driver alteration. Enrichment of mutations in CBL was replicated in published cohorts. Patients with RAS-mutated tumours and CBL deletions showed worse OS (p = 0.004) and RFS (p = 0.044). Point mutations in CBL were highly enriched in patients with NF1-mutated tumours, showing a trend (p = 0.18) towards worse OS.
conclusionsOur findings suggest CBL as a novel driver gene in melanoma, which is mutated in a relevant fraction of patients. Deletions of 11q23.1-3 including CBL were identified as a prognostic marker indicating a higher risk of recurrence and shorter survival. Furthermore, CBL could support patient stratification to identify high-risk patients who may benefit from adjuvant therapies or intensified monitoring strategies.
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