利用房水液活检描绘视网膜母细胞瘤的 DNA 甲基化特征。

Characterizing DNA methylation signatures of retinoblastoma using aqueous humor liquid biopsy.

机构信息

Department of Urology, University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, CA, 90033, USA.

Children's Hospital Los Angeles Vision Center & USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90027, USA.

出版信息

Nat Commun. 2022 Sep 21;13(1):5523. doi: 10.1038/s41467-022-33248-2.

Retinoblastoma (RB) is a cancer that forms in the developing retina of babies and toddlers. The goal of therapy is to cure the tumor, save the eye and maximize vision. However, it is difficult to predict which eyes are likely to respond to therapy. Predictive molecular biomarkers are needed to guide prognosis and optimize treatment decisions. Direct tumor biopsy is not an option for this cancer; however, the aqueous humor (AH) is an alternate source of tumor-derived cell-free DNA (cfDNA). Here we show that DNA methylation profiling of the AH is a valid method to identify the methylation status of RB tumors. We identify 294 genes directly regulated by methylation that are implicated in p53 tumor suppressor (RB1, p53, p21, and p16) and oncogenic (E2F) pathways. Finally, we use AH to characterize molecular subtypes that can potentially be used to predict the likelihood of treatment success for retinoblastoma patients.

视网膜母细胞瘤 (RB) 是一种在婴儿和幼儿发育中的视网膜中形成的癌症。治疗的目标是治愈肿瘤、挽救眼睛并最大限度地提高视力。然而，很难预测哪些眼睛可能对治疗有反应。需要预测性分子生物标志物来指导预后并优化治疗决策。对于这种癌症，直接进行肿瘤活检不是一种选择；然而，房水 (AH) 是肿瘤衍生的无细胞 DNA (cfDNA) 的另一种来源。在这里，我们表明，AH 的 DNA 甲基化分析是一种识别 RB 肿瘤甲基化状态的有效方法。我们确定了 294 个直接受甲基化调控的基因，这些基因与 p53 肿瘤抑制因子 (RB1、p53、p21 和 p16) 和致癌 (E2F) 途径有关。最后，我们使用 AH 来描述潜在可用于预测视网膜母细胞瘤患者治疗成功可能性的分子亚型。