4.7 Article

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

期刊

MOLECULAR ONCOLOGY
卷 16, 期 10, 页码 2071-2085

出版社

WILEY
DOI: 10.1002/1878-0261.13197

关键词

CellSearch; cfDNA; CTC; RMS; whole-exome sequencing

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资金

  1. Fondazione AIRC per la ricerca sul cancro (AIRC) [IG-15813, IG20052]

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Liquid biopsy analysis is a powerful and noninvasive tool for uncovering molecular features and disease progression in pediatric rhabdomyosarcoma patients. The study found that patients with metastatic disease have a higher number of circulating tumor cells compared to those with localized disease, while the detection of disseminated tumor cells is independent of disease presentation. Liquid biopsy can also provide information about the molecular makeup of primary tumors.
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.

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