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Tracing metastatic spread in pediatric solid tumors using copy number and targeted deep sequencing

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Titel: Tracing metastatic spread in pediatric solid tumors using copy number and targeted deep sequencing
Autoren: Andersson, Natalie, Ferro, Michele, Jansson, Caroline, Chattopadhyay, Subhayan, Karlsson, Jenny, Gisselsson, David
Weitere Verfasser: Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Clinical Genetics, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för klinisk genetik, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Clinical Genetics, Pathways of cancer cell evolution, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för klinisk genetik, Cancercellers evolution, Originator, Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Translational Cancer Research, Molecular Pediatric Oncology, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för translationell cancerforskning, Molekylär barnonkologi, Originator, Lund University, Faculty of Social Sciences, Departments of Administrative, Economic and Social Sciences, Lunds University Centre for Preparedness and Resilience, Lunds universitet, Samhällsvetenskapliga fakulteten, Samhällsvetenskapliga institutioner och centrumbildningar, LUPREP, Originator, Lund University, Profile areas and other strong research environments, Lund University Profile areas, LU Profile Area: Human rights, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Lunds universitets profilområden, LU profilområde: Mänskliga rättigheter, Originator
Quelle: Journal of Pathology. 267(3):1-19
Schlagwörter: Medical and Health Sciences, Clinical Medicine, Cancer and Oncology, Medicin och hälsovetenskap, Klinisk medicin, Cancer och onkologi
Beschreibung: The most common cause of death in pediatric cancer patients is a treatment-resistant tumor, compounded by metastatic spread, making surgery, radiation therapy, and chemotherapy unfeasible as curative treatment options. However, the mechanisms behind metastatic spread in pediatric tumors remain largely unexplored. We conducted whole-genome copy number profiling on 171 primary tumor and metastases samples from 17 patients with neuroblastoma, Wilms tumor, or gonadal tumors, and performed targeted deep sequencing on a subset. Phylogenetic reconstruction enabled spatiotemporal tracking of subclones. In total, 11 of 17 patients displayed at least one metastasis arising earlier, defined as occurring before the most recent common ancestor in the primary tumor. In eight patients, metastatic spread was observed several times during tumor evolution, with different subclones from the same primary tumor having metastatic capability, even colonizing the same site. Strikingly, dissemination between metastases (intermetastatic spread) occurred in eight of nine patients with metastases in at least two different sites, indicating that this is a common phenomenon in pediatric malignancy.
Zugangs-URL: https://doi.org/10.1002/path.6472
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  Data: Lund University, Profile areas and other strong research environments, Other Strong Research Environments, LUCC: Lund University Cancer Centre, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Övriga starka forskningsmiljöer, LUCC: Lunds universitets cancercentrum, Originator<br />Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Clinical Genetics, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för klinisk genetik, Originator<br />Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Clinical Genetics, Pathways of cancer cell evolution, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för klinisk genetik, Cancercellers evolution, Originator<br />Lund University, Faculty of Medicine, Department of Laboratory Medicine, Division of Translational Cancer Research, Molecular Pediatric Oncology, Lunds universitet, Medicinska fakulteten, Institutionen för laboratoriemedicin, Avdelningen för translationell cancerforskning, Molekylär barnonkologi, Originator<br />Lund University, Faculty of Social Sciences, Departments of Administrative, Economic and Social Sciences, Lunds University Centre for Preparedness and Resilience, Lunds universitet, Samhällsvetenskapliga fakulteten, Samhällsvetenskapliga institutioner och centrumbildningar, LUPREP, Originator<br />Lund University, Profile areas and other strong research environments, Lund University Profile areas, LU Profile Area: Human rights, Lunds universitet, Profilområden och andra starka forskningsmiljöer, Lunds universitets profilområden, LU profilområde: Mänskliga rättigheter, Originator
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  Data: The most common cause of death in pediatric cancer patients is a treatment-resistant tumor, compounded by metastatic spread, making surgery, radiation therapy, and chemotherapy unfeasible as curative treatment options. However, the mechanisms behind metastatic spread in pediatric tumors remain largely unexplored. We conducted whole-genome copy number profiling on 171 primary tumor and metastases samples from 17 patients with neuroblastoma, Wilms tumor, or gonadal tumors, and performed targeted deep sequencing on a subset. Phylogenetic reconstruction enabled spatiotemporal tracking of subclones. In total, 11 of 17 patients displayed at least one metastasis arising earlier, defined as occurring before the most recent common ancestor in the primary tumor. In eight patients, metastatic spread was observed several times during tumor evolution, with different subclones from the same primary tumor having metastatic capability, even colonizing the same site. Strikingly, dissemination between metastases (intermetastatic spread) occurred in eight of nine patients with metastases in at least two different sites, indicating that this is a common phenomenon in pediatric malignancy.
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