Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors.
Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors.
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DOI：
10.1038/s41698-023-00357-0
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发表时间：
2023-02-20
影响因子：
7.9
通讯作者：
中科院分区：
文献类型：
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作者：
我们设计了一种液体活检（LB）平台，采用低通全基因组测序（LP-WGS）和血浆无细胞（cf）DNA的靶向测序，以检测儿科实体瘤中的全基因组拷贝数改变（CNA）和基因融合。共分析了来自19名对照和73名患者的143份血浆样本，包括44例骨或软组织肉瘤和12例肾肿瘤、10例生殖细胞肿瘤、5例肝肿瘤和2例甲状腺肿瘤。从诊断时、治疗期间和治疗后和/或复发时收集的血浆中分离cfDNA。根据LP-WGS的CNA检测结果，诊断时入组的37例患者中有26例（70%）既往未接受过治疗（放疗、手术或化疗），其中包括27例局限性疾病患者中的18例（67%）和10例转移性疾病患者中的8例（80%）。对照组均未检测到体细胞CNA。在匹配的肿瘤中，通过LP-WGS鉴定的CNA与通过染色体微阵列分析检测的CNA具有高度一致性。用我们的下一代测序（NGS）面板OncoKids®在肿瘤样品中鉴定的突变也通过ctDNA的LP-WGS在26个血浆样品中的14个中检测到。最后，我们开发了一种基于杂交的捕获面板，分别针对尤文肉瘤或腺泡状横纹肌肉瘤（ARMS）患者的EWSR 1和FOXO 1融合。在12例尤文肉瘤患者中的10例和2例ARMS患者的血浆中检测到融合。总之，这些数据证明了我们的LB平台在评估患有各种实体瘤的儿科患者中的临床适用性。
We designed a liquid biopsy (LB) platform employing low-pass whole genome sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA from plasma to detect genome-wide copy number alterations (CNAs) and gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19 controls and 73 patients, including 44 bone or soft-tissue sarcomas and 12 renal, 10 germ cell, five hepatic, and two thyroid tumors. cfDNA was isolated from plasma collected at diagnosis, during and after therapy, and/or at relapse. Twenty-six of 37 (70%) patients enrolled at diagnosis without prior therapy (radiation, surgery, or chemotherapy) had circulating tumor DNA (ctDNA), based on the detection of CNAs from LP-WGS, including 18 of 27 (67%) patients with localized disease and eight of 10 (80%) patients with metastatic disease. None of the controls had detectable somatic CNAs. There was a high concordance of CNAs identified by LP-WGS to CNAs detected by chromosomal microarray analysis in the matching tumors. Mutations identified in tumor samples with our next-generation sequencing (NGS) panel, OncoKids®, were also detected by LP-WGS of ctDNA in 14 of 26 plasma samples. Finally, we developed a hybridization-based capture panel to target EWSR1 and FOXO1 fusions from patients with Ewing sarcoma or alveolar rhabdomyosarcoma (ARMS), respectively. Fusions were detected in the plasma from 10 of 12 patients with Ewing sarcoma and in two of two patients with ARMS. Combined, these data demonstrate the clinical applicability of our LB platform to evaluate pediatric patients with a variety of solid tumors.
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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：
11.1
作者：
Mouliere F;Smith CG;Heider K;Su J;van der Pol Y;Thompson M;Morris J;Wan JCM;Chandrananda D;Hadfield J;Grzelak M;Hudecova I;Couturier DL;Cooper W;Zhao H;Gale D;Eldridge M;Watts C;Brindle K;Rosenfeld N;Mair R
通讯作者：
Mair R
影响因子：
5.2
作者：
Kim ME;Polski A;Xu L;Prabakar RK;Peng CC;Reid MW;Shah R;Kuhn P;Cobrinik D;Hicks J;Berry JL
通讯作者：
Berry JL
影响因子：
5.2
作者：
通讯作者：
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影响因子：
5.2
作者：
Morini, Martina;Cangelosi, Davide;Varesio, Luigi
通讯作者：
Varesio, Luigi