The Vision Center at Children's Hospital Los Angeles, Los Angeles, Califorina, USA.
USC Roski Eye Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
Ophthalmic Genet. 2022 Dec;43(6):866-870. doi: 10.1080/13816810.2022.2142246. Epub 2022 Nov 7.
In patients with retinoblastoma, gains of chromosome 6p have been associated with less differentiated tumors. In cell-free DNA from the aqueous humor (AH), 6p gain has been associated with an increased risk of enucleation. While the identification of somatic copy number alterations (SCNAs) via the AH has been well established, these alterations are not routinely identified in the blood due to low tumor fraction.
SCNAs were considered positive at 20% deflection from the baseline. Somatic RB1 pathogenic variants were identified with targeted sequencing using a panel including all RB1 exons.
A 24-month-old patient presented with unilateral retinoblastoma (Group D/AJCC Stage cT2B) and was treated with primary enucleation. In the peripheral blood, a heterozygous mutation (c.3920T>A) in the APC gene was reported. Genomic analysis of the tumor and AH revealed two novel somatic RB1 mutations (c.1589_1590del and c.2330dupC). Both also demonstrated highly recurrent RB-related SCNAs. Chromosome 6p gain was detected in the blood with an amplitude suggesting approximately 12% tumor fraction. At a follow-up of 24 months, there has been no evidence of metastatic disease.
To our knowledge, this is the first time an SCNA has been detected in the blood of an RB patient, suggesting in some advanced eyes there may be a high enough tumor fraction to detect these alterations (>5% needed). It remains unclear whether 6p gain or increased tumor fraction in the blood is indicative of increased risk of metastatic disease or new primary cancer; studies to address this are ongoing.
在视网膜母细胞瘤患者中，6p 染色体获得与分化程度较低的肿瘤有关。在房水中的无细胞游离 DNA 中，6p 获得与眼球摘除风险增加有关。虽然通过房水识别体细胞拷贝数改变（SCNAs）已经得到很好的确立，但由于肿瘤分数低，这些改变在血液中通常无法识别。
SCNAs 被认为是偏离基线 20%的阳性。通过使用包括所有 RB1 外显子的面板进行靶向测序，鉴定体细胞 RB1 致病性变异。
一名 24 个月大的患者患有单侧视网膜母细胞瘤（D/AJCC 分期 cT2B），并接受了初次眼球摘除术。在外周血中，报告了 APC 基因中的杂合突变（c.3920T>A）。肿瘤和房水的基因组分析显示了两个新的体细胞 RB1 突变（c.1589_1590del 和 c.2330dupC）。两者均表现出高度重现的 RB 相关 SCNAs。在血液中检测到 6p 染色体获得，其幅度表明大约有 12%的肿瘤分数。在 24 个月的随访中，没有转移性疾病的证据。
据我们所知，这是首次在 RB 患者的血液中检测到 SCNA，表明在某些晚期眼中，可能有足够高的肿瘤分数来检测这些改变（需要>5%）。目前尚不清楚血液中的 6p 获得或肿瘤分数增加是否表明转移性疾病或新发原发性癌症的风险增加；正在进行解决这个问题的研究。
