Somatic Copy Number Alteration in Circulating Tumor DNA for Monitoring of Pediatric Patients with Cancer

• Published in: Biomedicines Vol. 11; no. 4; p. 1082
• Main Authors: Ruas, Juliana Silveira, Silva, Felipe Luz Torres, Euzébio, Mayara Ferreira, Biazon, Tássia Oliveira, Daiggi, Camila Maia Martin, Nava, Daniel, Franco, Mayra Troiani, Cardinalli, Izilda Aparecida, Cassone, Alejandro Enzo, Pereira, Luiz Henrique, Seidinger, Ana Luiza, Maschietto, Mariana, Jotta, Patricia Yoshioka
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-04-2023; MDPI
• Subjects: Biomarkers; Biopsy; Bone cancer; Cancer; Cancer patients; cell-free DNA; Children; circulating tumor DNA; Copy number; copy number alterations; Deoxyribonucleic acid; Diagnosis; digital PCR; DNA; DNA methylation; DNA sequencing; Ethylenediaminetetraacetic acid; Ewing's sarcoma; Ewings sarcoma; Genetic aspects; Genetic testing; Health aspects; Medical prognosis; Medical records; Metastases; Methods; MYCN; Nervous system; Neuroblastoma; Nucleotide sequencing; Osteosarcoma; Patients; Pediatrics; Peripheral blood; Plasma; Rhabdomyosarcoma; Sarcoma; Software; Teratoma; Tumor proteins; Tumors; Germany; United States > US; 1q; cell-free DNA; MYCN; digital PCR; copy number alterations; circulating tumor DNA
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11041082

Pediatric tumors share few recurrent mutations and are instead characterized by copy number alterations (CNAs). The cell-free DNA (cfDNA) is a prominent source for the detection of cancer-specific biomarkers in plasma. We profiled CNAs in the tumor tissues for further evaluation of alterations in 1q,
and 17p in the circulating tumor DNA (ctDNA) in the peripheral blood at diagnosis and follow-up using digital PCR. We report that among the different kinds of tumors (neuroblastoma, Wilms tumor, Ewing sarcoma, rhabdomyosarcoma, leiomyosarcoma, osteosarcoma and benign teratoma), neuroblastoma presented the greatest amount of cfDNA, in correlation with tumor volume. Considering all tumors, cfDNA levels correlated with tumor stage, metastasis at diagnosis and metastasis developed during therapy. In the tumor tissue, at least one CNA (at
,
, surrogate markers for 1q and 17p, respectively, and
) was observed in 89% of patients. At diagnosis, CNAs levels were concordant between tumor and ctDNA in 56% of the cases, and for the remaining 44%, 91.4% of the CNAs were present only in cfDNA and 8.6% only in the tumor. Within the cfDNA, we observed that 46% and 23% of the patients had
and 1q gain, respectively. The use of specific CNAs as targets for liquid biopsy in pediatric patients with cancer can improve diagnosis and should be considered for monitoring of the disease response.