Table 1.
Overview of proof-of-concept studies of liquid biopsies involving pediatric oncology patients
| Author | Tumor entity | Number of pediatric patients | Technique | Biomaterial | Method | Clinical application |
|---|---|---|---|---|---|---|
| Chicard [14] | Neuroblastoma | 70 | OncoScan Array (Affymetrix) | Plasma | CNA profiling | Therapeutic and risk stratification |
| Van Roy [68] | Neuroblastoma | 37 | sWGS | Plasma | CNA profiling | Therapeutic and risk stratification |
| Combaret [17] | Neuroblastoma | 114 | ddPCR | Plasma | ALK hotspot mutation | Diagnostic and therapeutic stratification |
| Combaret [18] | Neuroblastoma | 102 | PCR | Plasma, serum | MYCN amplification | Diagnostic and therapeutic stratification |
| Lodrini [41] | Neuroblastoma | 10 | ddPCR | Plasma | ALK and MYCN copy number status | Diagnosis and therapeutic stratification, Monitoring disease progression |
| Chicard [15] | Neuroblastoma | 19 | WES, ands targeted resequencing | Plasma | SNV and CNA profiling at different timepoints |
Identifying treatment-resistant clones, Longitudinal follow-up |
| Jimenez [33] | Renal tumors | 18 | WES | Plasma | Somatic SNV and CNA profiling at diagnosis | Improved molecular diagnosis |
| Ueno-Yokohata [67] | Clear cell sarcoma of the kidney | 4 | PCR | Plasma | Detection of internal tandem duplication of BCOR | Improved molecular diagnosis |
| Krumbholz [37] | Ewing sarcoma | 20 | ddPCR | Plasma | EWSR1 fusion gene detection | Therapy monitoring |
| Shukla [60] |
Ewing sarcoma, Desmoplastic small round cell tumor |
7 |
ddPCR, Targeted resequencing |
Plasma | ESWR1 fusion gene detection | Disease monitoring |
| Hayashi [30] | Ewing sarcoma | 3 | ddPCR | Plasma | EWS-ETS fusion gene detection | Therapy monitoring |
| Barris [4] | Osteosarcoma | 4 | Targeted resequencing | Plasma | Patient-specific alterations in 7 genes | Disease monitoring |
| Mussolin [49] | Hodgkin and NHL | 201 | qPCR | Plasma | Presence of cell free DNA | Improved diagnostics |
| Machado [43] | B-NHL | 30 | qPCR | Plasma | Total cell-free and EBV virus DNA quantification | Disease detection and treatment, response monitoring |
| Bruscaggin [9] | Hodgkin lymphoma | 44 | CAPP-Seq | Plasma | Genotyping of newly diagnosed and refractory HL | Disease monitoring |
| Primerano [55] | Hodgkin lymphoma | 155 | qPCR | Plasma | Cell-free DNA quantification | Disease detection and treatment Response monitoring |
| Berry [5] | Retinoblastoma | 6 | sWGS, Sanger | Vitreous fluid | CNA profiling, RB1 mutation detection | Surrogate for tumor biopsy after salvage therapy |
| Berry [6] | Retinoblastoma | 26 | sWGS | Vitreous fluid | CNA profiling | Therapy response monitoring |
| Huang [31] | Diffuse midline gliomas | 11 | Nested PCR, Sanger | CSF | Histone H3 gene mutation in CSF | Alternative or complementary to tissue diagnosis |
| Martinez-Ricarte [44] | Gliomas | 2 | Targeted sequencing, ddPCR | CSF | Detection of IDH1/2, TP53, ATRX, TERT, H3F3A, HIST1H3B gene mutations in CSF | Facilitating diagnosis of diffuse gliomas |
| Paret [53] | HGNET-BCOR | 1 | Patient-specific PCR + Sanger | Plasma | Follow-up of a BCOR internal tandem duplication | Personalized treatment and therapy monitoring |
| Klega [36] | Osteosarcoma, neuroblastoma, alveolar rhabdomyosarcoma, Wilms tumor | 45 | sWGS | Plasma | CNA and translocation characterization | Disease detection, Risk stratification, Treatment response monitoring |
| Weaver [74] | Gliomas | 10 | Methylation-specific PCR | Plasma | Promoter methylation detection | Disease monitoring |
CSF, cerebrospinal fluid; HGNET-BCOR, high-grade neuroepithelial tumor of the central nervous system with BCOR alteration; PCR, polymerase chain reaction; SNV, single-nucleotide variant; WES, whole-exome sequencing; qPCR, quantitative PCR; ddPCR, droplet digital PCR: CNA, copy number alterations; NHL, non-Hodgkin lymphoma; EBV, Epstein-Barr virus; sWGS, shallow whole-genome sequencing; SV, structural variant