Abstract B016: Identify DNA methylation signatures to predict chemo-resistance retinoblastoma in aqueous humor liquid biopsy

作者：Liya Xu, Emily Y. Lu, Daniel J. Weisenberger, Drishti Pandya, Hope Galarneau, Nerea Goni, David Cobrinik, Gangning Liang, Jesse L. Berry · 发表于：Cancer Research · 年份：2025 · DOI：10.1158/1538-7445.dnamethylation-b016 · 被引用次数：1 · 研究领域：Ocular Oncology and Treatments、Cancer-related Molecular Pathways、interferon and immune responses

Abstract Background: Retinoblastoma (RB) is the most common eye cancer in children, often leading to vision loss, enucleation, and potentially fatal outcomes if untreated. Due to the risk of cancer spread, direct tumor biopsy is not feasible, limiting opportunities for molecular diagnosis and prognosis. DNA methylation, a key epigenetic mechanism, regulates gene expression and plays a critical role in tumorigenesis by silencing tumor suppressor genes or activating oncogenes. This study aims to establish aqueous humor (AH) as a non-invasive liquid biopsy platform to capture DNA methylation markers reflective of RB tumor biology. By analyzing these profiles, we aim to identify epigenetic markers that differentiate high-risk RB cases from therapy-responsive ones, providing insights into tumor behavior and enabling precision-guided treatment strategies. Methods: Thirty-five AH samples from RB patients underwent DNA methylation profiling using the Illumina EPIC850 array, with methylation signatures correlated to clinical outcomes. Analysis included supervised clustering to identify distinct methylation patterns between salvaged and enucleated cases. Results: Supervised clustering revealed 895 significantly differentially methylated probes (∆β > 0.2 or < -0.2, p < 0.01) distinguishing salvaged eyes from enucleated eyes. Unsupervised clustering validated these distinct methylation signatures, with one active-treatment sample clustering with salvaged eyes and two...