Comprehensive Somatic Copy Number Analysis Using Aqueous Humor Liquid Biopsy for Retinoblastoma.
Comprehensive Somatic Copy Number Analysis Using Aqueous Humor Liquid Biopsy for Retinoblastoma.
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DOI：
10.3390/cancers13133340
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发表时间：
2021-07-03
期刊：
影响因子：
5.2
通讯作者：
Berry JL
中科院分区：
文献类型：
--
作者：
Kim ME;Polski A;Xu L;Prabakar RK;Peng CC;Reid MW;Shah R;Kuhn P;Cobrinik D;Hicks J;Berry JL
房水（AH）液体活检是视网膜母细胞瘤（RB）的无细胞循环肿瘤来源DNA的丰富来源。使用这种AH液体活检允许在没有肿瘤组织的情况下对眼睛进行基因组分析。该平台的开发至关重要，因为由于有眼外肿瘤扩散的风险，RB禁止直接肿瘤活检。在这项回顾性研究中，我们对64例RB患者68只眼睛的体细胞拷贝数改变（SCNAs）进行了全面的全基因组分析。我们发现，在需要立即去核（手术切除）的眼睛和试图挽救但随后治疗失败、需要二次去核的眼睛之间，特异性scna的患病率是不同的。染色体不稳定性的增加，或更多的广泛基因组改变，预示着这些眼睛的高风险临床和生物标志物特征。需要前瞻性分析来进一步确定这些发现的临床相关性和应用。房水（AH）液体活检已被确定为视网膜母细胞瘤（RB）的替代肿瘤活检。先前的AH研究主要集中在高复发性RB体细胞拷贝数改变（SCNAs）上，包括1q、2p、6p的增加以及13q和16q的缺失。在这项回顾性研究中，我们对2014年12月至2020年10月期间获得AH的64例RB患者的68只眼睛的RB SCNAs进行了全面的全基因组分析，并评估了相关的临床特征。对AH无细胞DNA进行浅全基因组测序以评估SCNAs。特异性非高复发性scna的患病率，如20q增加和8p损失，在原发性和继发性去核眼之间存在差异。染色体不稳定性的增加预示着更先进的种子形态（p = 0.015）；诊断年龄较晚（p < 0.0001）；内生肿瘤生长模式的几率更高（无视网膜脱离；p = 0.047）；肿瘤高度bbb10 mm (p = 0.09)；并且含有6p增益，这是眼部预后不良的生物标志物（p = 0.004）。AH液体活检平台是一种高产量的RB全基因组SCNA分析方法，SCNA与RB眼的许多临床表现有关。鼓励前瞻性分析进一步阐明特异性SCNAs在RB中的临床相关性。
Aqueous humor (AH) liquid biopsy is an enriched source of cell-free circulating tumor-derived DNA for retinoblastoma (RB). The use of this AH liquid biopsy allows for genomic analysis of eyes in the absence of tumor tissue. Development of this platform was critical because direct tumor biopsy is prohibited in RB due to risk of extraocular tumor spread. In this retrospective study, we provide comprehensive, whole-genome analysis of the somatic copy number alterations (SCNAs) in 68 eyes of 64 RB patients. We show that the prevalence of specific SCNAs differ between eyes that required immediate enucleation (surgical removal) and eyes that were attempted to be saved but subsequently failed treatment, requiring secondary enucleation. Increases in chromosomal instability, or higher number of broad genomic alterations, predict higher risk clinical and biomarker features in these eyes. Prospective analyses are needed to further determine the clinical relevance and application of these findings. 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 (p = 0.015); later age of diagnosis (p < 0.0001); greater odds of an endophytic tumor growth pattern (without retinal detachment; p = 0.047); tumor heights >10 mm (p = 0.09); and containing 6p gain, a biomarker of poor ocular prognosis (p = 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.
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影响因子：
5.2
作者：
Davies HR;Broad KD;Onadim Z;Price EA;Zou X;Sheriff I;Karaa EK;Scheimberg I;Reddy MA;Sagoo MS;Ohnuma SI;Nik-Zainal S
通讯作者：
Nik-Zainal S
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8
作者：
Grasemann, C;Gratias, S;Lohmann, DR
通讯作者：
Lohmann, DR
影响因子：
13.7
作者：
Amram, Alec L.;Rico, Grecia;Chevez-Barrios, Patricia
通讯作者：
Chevez-Barrios, Patricia
影响因子：
13.7
作者：
Berry, Jesse L.;Bechtold, Mercy;Kim, Jonathan W.
通讯作者：
Kim, Jonathan W.