Retinoblastoma (RB) is a childhood intraocular cancer initiated by biallelic inactivation of the RB tumor suppressor gene (RB1 ^−/−). RB can be hereditary (germline RB1 pathogenic allele is present) or non‐hereditary. Somatic copy number alterations (SCNAs) contribute to subsequent tumorigenesis. Previous studies of only enucleated RB eyes have reported associations between heritability status and the prevalence of SCNAs. Herein, we use an aqueous humor (AH) liquid biopsy to investigate RB genomic profiles in the context of germline RB1 status, age, and International Intraocular Retinoblastoma Classification (IIRC) clinical grouping for both enucleated and salvaged eyes. Between 2014 and 2019, AH was sampled from a total of 54 eyes of 50 patients. Germline RB1 status was determined from clinical blood testing, and cell‐free DNA from AH was analyzed for SCNAs. Of the 50 patients, 23 (46.0%; 27 eyes) had hereditary RB, and 27 (54.0%, 27 eyes) had non‐hereditary RB. Median age at diagnosis was comparable between hereditary (13 ± 10 months) and non‐hereditary (13 ± 8 months) eyes (P = 0.818). There was no significant difference in the prevalence or number of SCNAs based on (1) hereditary status (P  > 0.56) or (2) IIRC grouping (P  > 0.47). There was, however, a significant correlation between patient age at diagnosis, and (1) number of total SCNAs (r [52] = 0.672, P  < 0.00001) and (2) number of highly‐recurrent RB SCNAs (r [52] = 0.616, P  < 0.00001). This evidence does not support the theory that specific molecular or genomic subtypes exist between hereditary and non‐hereditary RB; rather, the prevalence of genomic alterations in RB eyes is strongly related to patient age at diagnosis.

中文翻译：

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视网膜母细胞瘤基因组稳定性的变异性受年龄而非遗传性驱动。

视网膜母细胞瘤 (RB) 是一种儿童眼内癌症，由 RB 肿瘤抑制基因 ( RB1 ^-/- )的双等位基因失活引发。RB 可以是遗传性的（存在种系RB1致病性等位基因）或非遗传性。体细胞拷贝数改变 (SCNA) 有助于随后的肿瘤发生。先前仅对去核 RB 眼的研究报告了遗传状态与 SCNA 流行之间的关联。在此，我们使用房水 (AH) 液体活检来研究生殖系RB1背景下的 RB 基因组谱摘除眼和抢救眼的状态、年龄和国际眼内视网膜母细胞瘤分类 (IIRC) 临床分组。2014 年至 2019 年期间，从 50 名患者的 54 只眼中对 AH 进行了采样。通过临床血液检测确定生殖系RB1状态，并分析来自 AH 的无细胞 DNA 的 SCNA。在 50 名患者中，23 名（46.0%；27 只眼）患有遗传性 RB，27 名（54.0%，27 只眼）患有非遗传性 RB。遗传性（13 ± 10 个月）和非遗传性（13 ± 8 个月）眼的诊断时中位年龄相当（P = 0.818）。基于 (1) 遗传状态 ( P  > 0.56) 或 (2) IIRC 分组 ( P > 0.47）。有，但是，患者年龄之间在诊断和总的SCNA的（1）号（一个显著的相关性，- [R [52] = 0.672，P  <0.00001）和高度经常RB的SCNA的（2）号（- [R [52] = 0.616，P  < 0.00001）。该证据不支持遗传性和非遗传性 RB 之间存在特定分子或基因组亚型的理论；相反，RB 眼中基因组改变的流行与诊断时的患者年龄密切相关。