Canadian journal of ophthalmology. Journal canadien d'ophtalmologie · 2026
Mutations with prognostic value in uveal melanoma: analytical study of variants detected by targeted next-generation sequencing.
СтатьяНаблюдательное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Pérez-Pérez Manuel, de Sola-Llamas Carmen García, Agostino Alessandro, Ruvolo Michael, Vilches-Arenas Angel, Relimpio-López M Isabel, Macías-García Laura, De Miguel-Rodríguez Manuel, Umbria-Jimenez Sebastian, García-Escudero Antonio, Idoate Miguel A, Ríos-Martín Juan J
Аннотация
OBJECTIVE: To identify genetic variants with prognostic value in uveal melanoma (UM) using targeted next-generation sequencing (NGS) and evaluate their association with metastasis and histologic subtype.
DESIGN: A retrospective observational study.
METHODS: Targeted NGS was performed on tumour samples from 69 patients with choroidal melanoma treated by enucleation. Histopathological features and clinical outcomes were reviewed. Cox regression and multivariable logistic regression analyses were used to assess the relationship between genetic variants and metastatic risk and histological subtype, respectively. Internal model validation was performed using bootstrap resampling.
RESULTS: A total of 231 pathogenic variants were identified across 28 genes. In multivariable Cox analysis, larger tumour size (HR = 3.07), and higher mitotic index (HR = 1.31) were significantly associated with increased metastatic risk, along with mutations in BAP1, CHEK2, and DICER1. Internal validation yielded a corrected Harrell's C-index score of 0.801. Logistic regression showed that BAP1 and LRP1B mutations were associated with epithelioid/mixed histology, while SF3B1 mutation was associated with spindle cell morphology.
CONCLUSIONS: Mutations in BAP1, CHEK2, and DICER1 are independently associated with poorer prognosis in UM, while SF3B1 defines a distinct histologic subgroup. Routine mutational profiling by targeted NGS may aid in risk stratification and follow-up of UM patients.
DESIGN: A retrospective observational study.
METHODS: Targeted NGS was performed on tumour samples from 69 patients with choroidal melanoma treated by enucleation. Histopathological features and clinical outcomes were reviewed. Cox regression and multivariable logistic regression analyses were used to assess the relationship between genetic variants and metastatic risk and histological subtype, respectively. Internal model validation was performed using bootstrap resampling.
RESULTS: A total of 231 pathogenic variants were identified across 28 genes. In multivariable Cox analysis, larger tumour size (HR = 3.07), and higher mitotic index (HR = 1.31) were significantly associated with increased metastatic risk, along with mutations in BAP1, CHEK2, and DICER1. Internal validation yielded a corrected Harrell's C-index score of 0.801. Logistic regression showed that BAP1 and LRP1B mutations were associated with epithelioid/mixed histology, while SF3B1 mutation was associated with spindle cell morphology.
CONCLUSIONS: Mutations in BAP1, CHEK2, and DICER1 are independently associated with poorer prognosis in UM, while SF3B1 defines a distinct histologic subgroup. Routine mutational profiling by targeted NGS may aid in risk stratification and follow-up of UM patients.