Circulating Cell-Free DNA Assessment in Biofluids from Children with Neuroblastoma Demonstrates Feasibility and Potential for Minimally Invasive Molecular Diagnostics.
Circulating Cell-Free DNA Assessment in Biofluids from Children with Neuroblastoma Demonstrates Feasibility and Potential for Minimally Invasive Molecular Diagnostics.
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手术活检的侵入性阻止了其连续应用于监测疾病。单次活检不能反映随时间变化的癌症动力学、肿瘤内异质性和药物敏感性。检测和表征实体瘤患者生物液中的无细胞循环肿瘤DNA可以更好地支持疾病监测，并为个性化医疗的临床决策提供先进的分子信息。在这里，我们研究了84名低、中、高危神经母细胞瘤婴儿和儿童的血液、骨髓、脑脊液和尿液中的游离DNA特征。我们报告了每种生物流体的特征尺寸分布和浓度模式，以提供信息来支持成功的液体活检生物库策略的发展。我们研究了疾病活动与cfDNA浓度之间的潜在相关性，并提供了强有力的证据，证明可以在婴儿的非常小的血液体积中检测到神经母细胞瘤特异性标志物。由于儿童患者体重较低，液体活检策略具有挑战性。本研究调查了来自84名神经母细胞瘤患者的血液、骨髓、脑脊液和尿液中cfDNA的大小分布和浓度，这些患者被分类为低风险（n = 28）、中等风险（n = 6）或高风险（n = 50），以提供液体活检生物库策略的关键数据。提供的血液和骨髓血浆的平均体积范围为1 - 2 mL。通过Agilent TapeStation测量获得的637个DNA电泳图的分析揭示了每种生物流体的五种不同的主要概况和特征DNA大小分布模式。主要含有cfDNA的样品比例为85.5%，是血浆中最高的。样品中的中值cfDNA浓度总计为6.28ng/mL（血浆）、58.2ng/mL（骨髓血浆）、0.08ng/mL（脑脊液）和0.49ng/mL（尿液）。数据集的荟萃分析表明，采用相同生物流体样品的多个基于cfDNA的测定最佳要求血液和骨髓血浆的采样体积为1 mL，脑脊液的采样体积为2 mL，尿液样品的采样体积尽可能大。对治疗的有利反应与高风险神经母细胞瘤患者中基于血液的cfDNA浓度的快速降低相关。基于血液的cfDNA浓度不足以作为指示高风险疾病复发的单一参数。我们提供的概念证明，监测成神经细胞瘤特异性标志物在非常小的血液体积从婴儿是可行的。
The invasive nature of surgical biopsies prevents their sequential application to monitor disease. Single biopsies fail to reflect cancer dynamics, intratumor heterogeneity, and drug sensitivities that change over time. Detection and characterization of cell-free circulating tumor DNA in biofluids from patients with solid tumors may better support disease monitoring and provide advanced molecular information for clinical decision-making toward personalized medicine. Here, we investigated the cell-free DNA characteristics in blood, bone marrow, cerebrospinal fluid, and urine provided from 84 infants and children with low-, intermediate-, or high-risk neuroblastoma. We report characteristic size distribution and concentration patterns for each biofluid to provide information to support the development of successful liquid biopsy biobanking strategies. We investigate potential correlations between disease activity and cfDNA concentration and provide strong evidence that markers specific for neuroblastoma can be detected in very small blood volumes from infants. Liquid biopsy strategies in pediatric patients are challenging due to low body weight. This study investigated cfDNA size distribution and concentration in blood, bone marrow, cerebrospinal fluid, and urine from 84 patients with neuroblastoma classified as low (n = 28), intermediate (n = 6), or high risk (n = 50) to provide key data for liquid biopsy biobanking strategies. The average volume of blood and bone marrow plasma provided ranged between 1 and 2 mL. Analysis of 637 DNA electropherograms obtained by Agilent TapeStation measurement revealed five different major profiles and characteristic DNA size distribution patterns for each of the biofluids. The proportion of samples containing primarily cfDNA was, at 85.5%, the highest for blood plasma. The median cfDNA concentration amounted to 6.28 ng/mL (blood plasma), 58.2 ng/mL (bone marrow plasma), 0.08 ng/mL (cerebrospinal fluid), and 0.49 ng/mL (urine) in samples. Meta-analysis of the dataset demonstrated that multiple cfDNA-based assays employing the same biofluid sample optimally require sampling volumes of 1 mL for blood and bone marrow plasma, 2 mL for cerebrospinal fluid, and as large as possible for urine samples. A favorable response to treatment was associated with a rapid decrease in blood-based cfDNA concentration in patients with high-risk neuroblastoma. Blood-based cfDNA concentration was not sufficient as a single parameter to indicate high-risk disease recurrence. We provide proof of concept that monitoring neuroblastoma-specific markers in very small blood volumes from infants is feasible.
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影响因子：
3.2
作者：
Combaret, Valerie;Hogarty, Michael D.;Puisieux, Alain
通讯作者：
Puisieux, Alain
DOI：
10.1007/s40272-017-0251-3
发表时间：
2017-12
期刊：
Paediatric drugs
影响因子：
--
作者：
Berthold F;Spix C;Kaatsch P;Lampert F
通讯作者：
Lampert F
影响因子：
4.6
作者：
Klega K;Imamovic-Tuco A;Ha G;Clapp AN;Meyer S;Ward A;Clinton C;Nag A;Van Allen E;Mullen E;DuBois SG;Janeway K;Meyerson M;Thorner AR;Crompton BD
通讯作者：
Crompton BD
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
5.2
作者：
Kahana-Edwin S;Cain LE;McCowage G;Darmanian A;Wright D;Mullins A;Saletta F;Karpelowsky J
通讯作者：
Karpelowsky J