Clinical significance of circulating tumor cells and cell-free DNA in pediatric rhabdomyosarcoma,Molecular Oncology

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Clinical significance of circulating tumor cells and cell-free DNA in pediatric rhabdomyosarcoma
Molecular Oncology ( IF 5.0 ) Pub Date : 2022-02-24 , DOI: 10.1002/1878-0261.13197
Lucia Tombolan _{1,

2} , Elisabetta Rossi _{3,

4} , Andrea Binatti ₅ , Angelica Zin ₁ , Mariangela Manicone ₄ , Antonella Facchinetti _{3,

4} , Silvia Lucchetta ₂ , Maria Carmen Affinita ₂ , Paolo Bonvini ₁ , Stefania Bortoluzzi ₅ , Rita Zamarchi ₄ , Gianni Bisogno ₂

Affiliation

Liquid biopsy analysis represents a powerful and noninvasive tool to uncover biomarkers for disseminated disease assessment and longitudinal monitoring of patients. Herein, we explored the value of circulating and disseminated tumor cells (CTC and DTC, respectively) and cell-free DNA (cfDNA) in pediatric rhabdomyosarcoma (RMS). Peripheral blood and bone marrow samples were analyzed to detect and enumerate CTC and DTC, respectively. We used the epithelial cellular adhesion molecule (EpCAM)-based CellSearch platform coupled with an automatic device to collect both EpCAM-positive and EpCAM-low/negative CTCs. The standard assay was implemented, including the mesenchymal marker desmin. For selected cases, we molecularly profiled primary tumors and liquid biopsy biomarkers using whole-exome sequencing and droplet digital PCR, respectively. RMS patients with metastatic disease had a significantly higher number of CTCs compared to those with localized disease, whereas DTCs were detected independently of disease presentation. The use of the desmin marker remarkably increased the identification of CTCs and DTCs in RMS samples. Of note, CTC clusters were detected in RMS patients with disseminated disease. Further, cfDNA and CTC molecular features closely reflected the molecular makeup of primary tumors and informed of disease course.

中文翻译：

小儿横纹肌肉瘤循环肿瘤细胞和游离DNA的临床意义

液体活检分析代表了一种强大的非侵入性工具，可以发现用于传播疾病评估和患者纵向监测的生物标志物。在此，我们探讨了循环和播散性肿瘤细胞（分别为 CTC 和 DTC）和游离 DNA（cfDNA）在小儿横纹肌肉瘤 (RMS) 中的价值。分析外周血和骨髓样本以分别检测和计数 CTC 和 DTC。我们使用基于上皮细胞粘附分子 (EpCAM) 的 CellSearch 平台以及自动装置来收集 EpCAM 阳性和 EpCAM 低/阴性 CTC。实施标准测定，包括间充质标记结蛋白。对于选定的病例，我们分别使用全外显子组测序和液滴数字 PCR 对原发性肿瘤和液体活检生物标志物进行分子分析。与患有局部疾病的患者相比，患有转移性疾病的 RMS 患者的 CTC 数量显着增加，而 DTC 的检测与疾病表现无关。结蛋白标记的使用显着增加了 RMS 样品中 CTC 和 DTC 的鉴定。值得注意的是，在患有播散性疾病的 RMS 患者中检测到 CTC 簇。此外，cfDNA 和 CTC 分子特征密切反映了原发性肿瘤的分子组成，并为病程提供了信息。

更新日期：2022-02-24

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