Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors

npj Precision Oncology, Journal Year: 2023, Volume and Issue: 7(1)

Published: Feb. 20, 2023

Abstract We designed a liquid biopsy (LB) platform employing low-pass whole genome sequencing (LP-WGS) and targeted of cell-free (cf) DNA from plasma to detect genome-wide copy number alterations (CNAs) gene fusions in pediatric solid tumors. A total 143 samples were analyzed 19 controls 73 patients, including 44 bone or soft-tissue sarcomas 12 renal, 10 germ cell, five hepatic, two thyroid cfDNA was isolated collected at diagnosis, during after therapy, and/or relapse. Twenty-six 37 (70%) patients enrolled diagnosis without prior therapy (radiation, surgery, chemotherapy) had circulating tumor (ctDNA), based on the detection CNAs LP-WGS, 18 27 (67%) with localized disease eight (80%) metastatic disease. None detectable somatic CNAs. There high concordance identified by LP-WGS detected chromosomal microarray analysis matching Mutations our next-generation (NGS) panel, OncoKids®, also ctDNA 14 26 samples. Finally, we developed hybridization-based capture panel target EWSR1 FOXO1 Ewing sarcoma alveolar rhabdomyosarcoma (ARMS), respectively. Fusions ARMS. Combined, these data demonstrate clinical applicability LB evaluate variety

Language: Английский

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A comprehensive overview of liquid biopsy applications in pediatric solid tumors

npj Precision Oncology, Journal Year: 2024, Volume and Issue: 8(1)

Published: Aug. 3, 2024

Abstract Liquid biopsies are emerging as an alternative source for pediatric cancer biomarkers with potential applications during all stages of patient care, from diagnosis to long-term follow-up. While developments within this field reported, these mainly focus on dedicated items such a specific liquid biopsy matrix, analyte, and/or single tumor type. To the best our knowledge, comprehensive overview is lacking. Here, we review current state research most common non-central nervous system solid tumors. These include neuroblastoma, renal tumors, germ cell osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas, liver Within selection, discuss important or recent studies involving biopsy-based biomarkers, anticipated clinical applications, challenges success. Furthermore, provide biomarker publication output each type based literature search between 1989 2023. Per study identified, list relevant matrices (e.g., peripheral blood, bone marrow, cerebrospinal fluid), analytes circulating cell-free DNA, microRNAs, cells), methods digital droplet PCR next-generation sequencing), involved cohort, proposed applications. As such, identified 344 unique publications. Taken together, while in oncology still behind adult oncology, potentially publications have increased over last decade. Importantly, steps towards implementation rapidly gaining ground, notably through validation trials.

Language: Английский

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Precision medicine in diagnosis, prognosis, and disease monitoring of bone and soft tissue sarcomas using liquid biopsy: a systematic review

Archives of Orthopaedic and Trauma Surgery, Journal Year: 2025, Volume and Issue: 145(1)

Published: Jan. 11, 2025

Abstract Introduction Liquid biopsy as a non-invasive method to investigate cancer biology and monitor residual disease has gained significance in clinical practice over the years. Whilst its applicability carcinomas is well established, low incidence heterogeneity of bone soft tissue sarcomas explains less well-established knowledge considering liquid these highly malignant mesenchymal neoplasms. Materials methods A systematic literature review adhering PRISMA guidelines initially identified 920 studies, whom 68 original articles could be finally included, all dealing with sarcoma. Studies were discussed within two main chapters, i.e. translocation-associated complex-karyotype sarcomas. Results Overall, data on 2636 patients > 10 different entities summarised. The five most frequent tumour included osteosarcoma (n = 602), Ewing sarcoma 384), gastrointestinal stromal (GIST; n 203), rhabdomyosarcoma 193), leiomyosarcoma 145). Of 11 analytes, largest evidence was present for ctDNA cfDNA, investigated 26 18 respectively. Conclusions This provides an extensive up-to-date overview about current potential future uses modalities diagnostic, prognostic, monitoring markers

Language: Английский

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Liquid biopsy‐based circulating tumour (ct)DNA analysis of a spectrum of myeloid and lymphoid malignancies yields clinically actionable results

Histopathology, Journal Year: 2024, Volume and Issue: 84(7), P. 1224 - 1237

Published: Feb. 29, 2024

Aims Liquid biopsy (LBx)‐based next‐generation sequencing (NGS) of circulating tumour DNA (ctDNA) can facilitate molecular profiling haematopoietic neoplasms (HNs), particularly when tissue‐based NGS is infeasible. Methods and Results We studied HN LBx samples tested with FoundationOne CDx, Liquid, or FoundationACT between July 2016 March 2022. identified 271 samples: 89 non‐Hodgkin lymphoma (NHL), 43 plasma‐cell neoplasm (PCN), 41 histiocytoses, 27 myelodysplastic syndrome (MDS), 25 diffuse large B‐cell (DLBCL), 22 myeloproliferative (MPN), 14 Hodgkin (HL), 10 acute myeloid leukaemia (AML). Among 73.4% detectable pathogenic alterations, median maximum somatic allele frequency (MSAF) was 16.6%, AML (36.2%), MDS (19.7%), MPN (44.5%) having higher MSAFs than DLBCL (3.9%), NHL (8.4%), HL (1.5%), PCN (2.8%), histiocytoses (1.8%) ( P = 0.001). detected characteristic alterations across HNs, including in TP53 , KRAS MYD88 BTK NHLs; NRAS BRAF PCNs; IGH DLBCL; ATM PDCD1LG2 HL; MAP2K1 histiocytoses; SF3B1 DNMT3A TET2 ASXL1 MDS; JAK2 MPNs; FLT3 IDH2 NPM1 AML. 24 samples, the positive percent agreement by 75.7% for variants present paired buffy coat, marrow, tissues. Also, 75.0% pairs exhibited only on LBx. These were predominantly subclonal (clonal fraction 3.8%), reflecting analytical sensitivity Conclusion data demonstrate that detect relevant genomic at low clonal fractions, suggesting a potential clinical utility identifying residual emerging therapy‐resistant clones may be undetectable site‐specific tissue biopsies.

Language: Английский

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Clinical trial inclusion in patients with relapsed/refractory neuroblastoma following the European Precision Cancer Medicine trial MAPPYACTS

European Journal of Cancer, Journal Year: 2024, Volume and Issue: 201, P. 113923 - 113923

Published: Feb. 15, 2024

Language: Английский

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Precision Oncology in Pediatric Cancer Surgery

Surgical Oncology Clinics of North America, Journal Year: 2023, Volume and Issue: 33(2), P. 409 - 446

Published: Dec. 26, 2023

Language: Английский

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Metastatic Melanoma in Young Child

Journal of Pediatric Hematology/Oncology, Journal Year: 2023, Volume and Issue: 45(8), P. 461 - 462

Published: March 20, 2023

Pediatric melanoma is a rare cancer, especially in young children, and it remains diagnostic challenge. We report case of massively metastatic patient with an atypical clinical biological presentation no risk factors.

Language: Английский

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Comparison of Comprehensive Genomic Profiling Testing “Ion Torrent Genexus Sequencer” with FoundationOne

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 29, 2024

Abstract Background Molecular diagnostic tests are becoming increasingly routine, and the use of tissue- blood-based next-generation sequencing (NGS) is integral to delivery personalized medicine for targeted cancer therapy. This study aimed evaluate variant concordance somatic variants using two clinical NGS systems conducting both analyses: Genexus-OCA v3 (OCA) vs. FoundationOne CDx (F1) tissues Genexus OPA (OPA) Liquid (F1L) blood. Methods The genomic alterations between analyses was compared in six patients with breast, head, neck cancers tissue circulating tumor DNA biopsies. Results A total 130 genes were common F1 OCA, 41 F1L OPA. When comparing genes, sensitivity specificity OCA 55% 99%, respectively. Nine single-nucleotide (SNVs), one copy number alteration (CNA), fusion detected by FoundationOne. However, SNV ( MAP2K1 F53V), CNAs AKT3 MYC ), ESR-CCDC170 ) only Genexus, whereas SNVs TP53 Q331* KRAS G12V) Conclusion genome panels equivalent but not perfect terms detection blood, indicating that different assays analytical methods may have influenced results. performing comprehensive profilings (CGPs), it important consider characteristics each NGS-based CGP test genetic associated disease.

Language: Английский

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Clinical impact of large genomic explorations at diagnosis in 198 pediatric solid tumors: a monocentric study aiming practical feasibility of precision oncology

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: Oct. 21, 2024

Faced to the growing development of collecting systematic molecular analyses in relapsed pediatric cancers transform their targeted matched therapies, this study aimed assess clinical and therapeutic indications diagnostic genomic explorations performed solid determine which type screening if it afford at relapse time an accurate strategy. A total 280 patients less than 22 years, referred University Hospitals Strasbourg for a newly diagnosed tumor from January 2015 December 2021, were prospectively genomically investigated since diagnosis. Using 7 different tests going single-gene methods (IHC, FISH, RT-PCR, Sanger sequencing, droplet digital PCR) largescale (Next-Generation RNAsequencing FoundationOne®CDx), we explored retrospectively findings those tumors (except hematolymphoid cancers) improve diagnosis, prognosis assessment therapeutics. One hundred ninety-eight (71%) underwent biology (MB) Thirty-eight histologies grouped into cerebral (30%), sarcomas (26%, bone soft tissues), various blastomas (27%), other entities (17%). Over median 40-month follow-up, overall survival rate was 85% 28%. Of 326 carried out, 245 abnormalities (single nucleotide variations: 50%, fusions: 25%, copy number alteration: 20%) concerning 70 oncogenes highlighted. The impact 84%. Broad-spectrum had higher (57%) (28%). 75% broad-spectrum found actionable variant conducting 23% receive rapidly therapy first relapse. Our experience highlighted utility profiling as soon diagnosis children expect improving access innovative agents

Language: Английский

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