Simultaneous Copy Number Alteration and Single-Nucleotide Variation Analysis in Matched Aqueous Humor and Tumor Samples in Children with Retinoblastoma.
Simultaneous Copy Number Alteration and Single-Nucleotide Variation Analysis in Matched Aqueous Humor and Tumor Samples in Children with Retinoblastoma.
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视网膜母细胞瘤儿童中匹配的水性幽默和肿瘤样本中的同时拷贝数改变和单核苷酸变异分析。
DOI：
10.3390/ijms24108606
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发表时间：
2023-05-11
影响因子：
5.6
通讯作者：
Berry, Jesse L.
中科院分区：
文献类型：
--
作者：
Schmidt, Michael J.;Prabakar, Rishvanth K.;Pike, Sarah;Yellapantula, Venkata;Peng, Chen-Ching;Kuhn, Peter;Hicks, James;Xu, Liya;Berry, Jesse L.
关键词：
视网膜母细胞瘤（RB）是一种在幼儿视网膜发育中形成的儿童癌症;由于有引起眼外肿瘤扩散的风险，这种肿瘤不能进行活检，这极大地改变了患者的治疗和生存。最近，眼前房中的透明液体--房水（AH）已被开发为器官特异性液体活检，用于研究在生物流体的无细胞DNA（cfDNA）中发现的体内肿瘤来源的信息。然而，鉴定体细胞基因组改变，包括RB 1基因的体细胞拷贝数改变（SCNA）和单核苷酸变异（SNV），通常需要：（1）两种不同的实验方案-SCNA的低通全基因组测序和SNV的靶向测序-或（2）昂贵的深度全基因组或外显子组测序。为了节省时间和成本，我们应用一步靶向测序方法来鉴定RB儿童中的SCNA和RB 1 SNV。在比较靶向测序得到的SCNA调用与传统的低通全基因组测序方法时观察到高度一致性（中位数= 96.2%）。我们进一步应用该方法研究了来自11只RB眼睛的配对肿瘤和AH样本之间基因组改变的一致性程度。我们发现11/11个AH样本（100%）具有SCNA，其中10个（90.1%）具有复发性RB-SCNA，而11个肿瘤样本中只有9个（81.8%）在低通和靶向方法中具有阳性RB-SCNA特征。检测到的9个SNV中有8个（88.9%）在AH和肿瘤样品之间共享。最终，11/11例患者发现了体细胞改变，包括9例RB 1 SNV和10例复发性RB-SCNA，其中4例为局灶性RB 1缺失，1例为MYCN获得。所呈现的结果显示了利用一种测序方法来获得SCNA和靶向SNV数据以捕获RB疾病的广泛基因组范围的可行性，这可能最终加速临床干预并且比其他方法更便宜。
Retinoblastoma (RB) is a childhood cancer that forms in the developing retina of young children; this tumor cannot be biopsied due to the risk of provoking extraocular tumor spread, which dramatically alters the treatment and survival of the patient. Recently, aqueous humor (AH), the clear fluid in the anterior chamber of the eye, has been developed as an organ-specific liquid biopsy for investigation of in vivo tumor-derived information found in the cell-free DNA (cfDNA) of the biofluid. However, identifying somatic genomic alterations, including both somatic copy number alterations (SCNAs) and single nucleotide variations (SNVs) of the RB1 gene, typically requires either: (1) two distinct experimental protocols—low-pass whole genome sequencing for SCNAs and targeted sequencing for SNVs—or (2) expensive deep whole genome or exome sequencing. To save time and cost, we applied a one-step targeted sequencing method to identify both SCNAs and RB1 SNVs in children with RB. High concordance (median = 96.2%) was observed in comparing SCNA calls derived from targeted sequencing to the traditional low-pass whole genome sequencing method. We further applied this method to investigate the degree of concordance of genomic alterations between paired tumor and AH samples from 11 RB eyes. We found 11/11 AH samples (100%) had SCNAs, and 10 of them (90.1%) with recurrent RB-SCNAs, while only nine out of 11 tumor samples (81.8%) had positive RB-SCNA signatures in both low-pass and targeted methods. Eight out of the nine (88.9%) detected SNVs were shared between AH and tumor samples. Ultimately, 11/11 cases have somatic alterations identified, including nine RB1 SNVs and 10 recurrent RB-SCNAs with four focal RB1 deletions and one MYCN gain. The results presented show the feasibility of utilizing one sequencing approach to obtain SCNA and targeted SNV data to capture a broad genomic scope of RB disease, which may ultimately expedite clinical intervention and be less expensive than other methods.
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影响因子：
12.3
作者：
Kuilman T;Velds A;Kemper K;Ranzani M;Bombardelli L;Hoogstraat M;Nevedomskaya E;Xu G;de Ruiter J;Lolkema MP;Ylstra B;Jonkers J;Rottenberg S;Wessels LF;Adams DJ;Peeper DS;Krijgsman O
通讯作者：
Krijgsman O
影响因子：
3.7
作者：
Dunn P;Albury CL;Maksemous N;Benton MC;Sutherland HG;Smith RA;Haupt LM;Griffiths LR
通讯作者：
Griffiths LR
影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
4.2
作者：
Dimaras H;Corson TW
通讯作者：
Corson TW
影响因子：
7.9
作者：
通讯作者：
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