Kim Mary E, Polski Ashley, Xu Liya, Prabakar Rishvanth K, Peng Chen-Ching, Reid Mark W, Shah Rachana, Kuhn Peter, Cobrinik David, Hicks James, Berry Jesse L
The Vision Center at Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90033, USA.
Cancers (Basel). 2021 Jul 3;13(13):3340. doi: 10.3390/cancers13133340.
Aqueous humor (AH) liquid biopsy has been established as a surrogate tumor biopsy for retinoblastoma (RB). Previous AH studies have focused on highly recurrent RB somatic copy number alterations (SCNAs) including gain of 1q, 2p, 6p, and loss of 13q and 16q. In this retrospective study, we provide a comprehensive, whole-genome analysis of RB SCNAs and evaluate associated clinical features for 68 eyes of 64 RB patients from whom AH was obtained between December 2014 and October 2020. Shallow whole-genome sequencing of AH cell-free DNA was performed to assess for SCNAs. The prevalence of specific non-highly recurrent SCNAs, such as 20q gain and 8p loss, differed between primarily and secondarily enucleated eyes. Increases in chromosomal instability predict more advanced seeding morphology ( = 0.015); later age of diagnosis ( < 0.0001); greater odds of an endophytic tumor growth pattern (without retinal detachment; = 0.047); tumor heights >10 mm ( = 0.09); and containing 6p gain, a biomarker of poor ocular prognosis ( = 0.004). The AH liquid biopsy platform is a high-yield method of whole-genome RB SCNA analysis, and SCNAs are associated with numerous clinical findings in RB eyes. Prospective analyses are encouraged to further elucidate the clinical relevance of specific SCNAs in RB.
房水（AH）液体活检已被确立为视网膜母细胞瘤（RB）的替代肿瘤活检方法。先前的房水研究主要集中在RB高度复发性体细胞拷贝数改变（SCNA），包括1q、2p、6p增益以及13q和16q缺失。在这项回顾性研究中，我们对64例RB患者的68只眼睛进行了全面的全基因组RB SCNA分析，并评估了相关临床特征，这些患者的房水样本于2014年12月至2020年10月期间采集。对房水游离DNA进行浅层全基因组测序以评估SCNA。特定非高度复发性SCNA（如20q增益和8p缺失）的患病率在原发性和继发性眼球摘除眼中有所不同。染色体不稳定性增加预示着更晚期的播散形态（P = 0.015）；诊断年龄较大（P < 0.0001）；内生性肿瘤生长模式的可能性更大（无视网膜脱离；P = 0.047）；肿瘤高度>10 mm（P = 0.09）；以及含有6p增益，这是眼部预后不良的生物标志物（P = 0.004）。房水液体活检平台是全基因组RB SCNA分析的高产方法，且SCNA与RB眼中的众多临床发现相关。鼓励进行前瞻性分析以进一步阐明RB中特定SCNA的临床相关性。
