Circulating tumor DNA sequencing of pediatric solid and brain tumor patients: An institutional feasibility study.

Autor: Mangum R; Center for Cancer and Blood Disorders, Phoenix Children's Hospital, Phoenix, Arizona, USA., Reuther J; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA., Sen Baksi K; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA., Gandhi I; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA., Zabriskie RC; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA., Recinos A; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA., Raesz-Martinez R; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA., Lin FY; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.; The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA., Potter SL; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.; Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA., Sher AC; Department of Radiology, Texas Children's Hospital, Houston, Texas, USA., Kralik SF; Department of Radiology, Texas Children's Hospital, Houston, Texas, USA., Mohila CA; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.; Department of Pathology, Texas Children's Hospital, Houston, Texas, USA., Chintagumpala MM; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.; The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA., Muzny D; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; The Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA., Hu J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; The Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA., Gibbs RA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; The Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA., Fisher KE; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.; The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Pathology, Texas Children's Hospital, Houston, Texas, USA., Bernini JC; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA., Gill J; Division of Pediatrics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Griffin TC; Department of Hematology Oncology, The Children's Hospital of San Antonio, Baylor College of Medicine, San Antonio, Texas, USA., Tomlinson GE; Greehey Children's Cancer Research Institute, UT Health San Antonio, San Antonio, Texas, USA., Vallance KL; Hematology and Oncology, Cook Children's Medical Center, Fort Worth, Texas, USA., Plon SE; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.; The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; The Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA., Roy A; Department of Pathology & Immunology, Baylor College of Medicine, Houston, Texas, USA.; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.; The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Pathology, Texas Children's Hospital, Houston, Texas, USA., Parsons DW; Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.; The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas, USA.; Department of Pathology, Texas Children's Hospital, Houston, Texas, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.; The Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: Pediatric hematology and oncology [Pediatr Hematol Oncol] 2023; Vol. 40 (8), pp. 719-738. Date of Electronic Publication: 2023 Jun 27.
DOI: 10.1080/08880018.2023.2228837
Abstrakt: The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) of these initial samples. Twenty-four patients were identified whose tumors harbored 30 unique variants that were potentially detectable on a commercially-available ctDNA panel. Twenty of these 30 mutations (67%) were successfully detected by next-generation sequencing in the ctDNA from at least one plasma sample. The rate of ctDNA mutation detection was higher in patients with non-CNS solid tumors (7/9, 78%) compared to those with CNS tumors (9/15, 60%). A higher ctDNA mutation detection rate was also observed in patients with metastatic disease (9/10, 90%) compared to non-metastatic disease (7/14, 50%), although tumor-specific variants were detected in a few patients in the absence of radiographic evidence of disease. This study illustrates the feasibility of incorporating longitudinal ctDNA analysis into the management of relapsed or refractory patients with childhood CNS or non-CNS solid tumors.
Databáze: MEDLINE