Discovery of actionable genetic alterations with targeted panel sequencing in children with relapsed or refractory solid tumors

Autoři: Ji Won Lee aff001;  Nayoung K. D. Kim aff002;  Soo Hyun Lee aff004;  Hee Won Cho aff001;  Youngeun Ma aff001;  Hee Young Ju aff001;  Keon Hee Yoo aff001;  Ki Woong Sung aff001;  Hong Hoe Koo aff001;  Woong-Yang Park aff002
Působiště autorů: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea aff001;  Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea aff002;  Geninus Inc., Seoul, Korea aff003;  Department of Translational Molecular Pathology, MD Anderson Cancer Center, University of Texas, Houston, Texas, United States of America aff004;  Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea aff005;  Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea aff006
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224227


Advances in genomic technologies and the development of targeted therapeutics are making the use of precision medicine increasingly possible. In this study, we explored whether precision medicine can be applied for the management of refractory/relapsed pediatric solid tumors by discovering actionable alterations using targeted panel sequencing. Samples of refractory/relapsed pediatric solid tumors were tested using a targeted sequencing panel covering the exonic DNA sequences of 381 cancer genes and introns across 22 genes to detect clinically significant genomic aberrations in tumors. The molecular targets were tiered from 1 to 5 based on the presence of actionable genetic alterations, strength of supporting evidence, and drug availability in the Republic of Korea. From January 2016 to October 2018, 55 patients were enrolled. The median time from tissue acquisition to drug selection was 29 d (range 14–39), and tumor profiling was successful in 53 (96.4%) patients. A total of 27 actionable alterations in tiers 1–4 were detected in 20 patients (36.4%), and the majority of actionable alterations were copy number variations. The tiers of molecular alterations were tier 1 (clinical evidence) in 4 variants, tier 2 (preclinical evidence) in 8 variants, tier 3 (consensus opinion) in 2 variants, and tier 4 (actionable variants with a drug that is available in other countries but not in the Republic of Korea) in 9 variants. In one patient with relapsed neuroblastoma with ALK F1174L mutation and ALK amplification, lorlatinib was used in a compassionate use program, and it showed some efficacy. In conclusion, using a targeted sequencing panel to discover actionable alterations in relapsed/refractory pediatric solid tumors was practical and feasible.

Klíčová slova:

Cancer genomics – Gene sequencing – Genomic databases – Genomic medicine – Human genetics – Pediatrics – Neuroblastoma – Precision medicine


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2019 Číslo 11