1. The feasibility of using liquid biopsies as a complementary assay for copy number aberration profiling in routinely collected paediatric cancer patient samples
- Author
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Malaïka Van der Linden, Bram De Wilde, Marek Grega, Yasmine Iddir, Genevieve Laureys, Godelieve A.M. Tytgat, Janine Stutterheim, Andries De Koker, Frank Speleman, Mathieu Chicard, Lieke M. J. van Zogchel, Nadine Van Roy, Katleen De Preter, Ales Vicha, Christine Devalck, Gudrun Schleiermacher, Ruben Van Paemel, Leen Willems, Jolien Van Thorre, Jo Van Dorpe, Björn Menten, Charlotte Vandeputte, Lennart Raman, Tim Lammens, Jilke De Wilde, Nathalie S. M. Lak, Landsteiner Laboratory, CCA - Imaging and biomarkers, and Paediatric Oncology
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Adolescent ,DNA Copy Number Variations ,Tumour heterogeneity ,Concordance ,CLASSIFICATION ,Internal medicine ,Neuroblastoma ,MYCN ,Medicine and Health Sciences ,Biomarkers, Tumor ,medicine ,Humans ,HETEROGENEITY ,Prospective Studies ,Copy number aberrations ,cfDNA ,Liquid biopsy ,Child ,Rhabdomyosarcoma ,Retrospective Studies ,liquid biopsy ,LANDSCAPE ,business.industry ,Biomarker ,medicine.disease ,TUMORS ,pediatric cancer ,Biomarker (cell) ,Shallow whole-genome sequencing ,CELL-FREE DNA ,Child, Preschool ,NEUROBLASTOMA ,Feasibility Studies ,Osteosarcoma ,Female ,Sarcoma ,business ,Cell-Free Nucleic Acids - Abstract
Background: Paediatric tumours are often characterised by the presence of recurrent DNA copy number alterations (CNAs). These DNA copy number profiles, obtained from a tissue biopsy, can aid in the correct prognostic classification and therapeutic stratification of several paediatric cancer entities (e.g. MYCN amplification in neuroblastoma) and are part of the routine diagnostic practice. Liquid biopsies (LQBs) offer a potentially safer alternative for such invasive tumour tissue biopsies and can provide deeper insight into tumour heterogeneity. Procedure: The robustness and reliability of LQB CNA analyses was evaluated. We performed retrospective CNA profiling using shallow whole-genome sequencing (sWGS) on paired plasma circulating cell-free DNA (cfDNA) and tissue DNA samples from routinely collected samples from paediatric patients (n = 128) representing different tumour entities, including osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, Wilms tumour, brain tumours and neuroblastoma. Results: Overall, we observed a good concordance between CNAs in tissue DNA and cfDNA. The main cause of CNA discordance was found to be low cfDNA sample quality (i.e. the ratio of cfDNA (700 bp)). Furthermore, CNAs were observed that were present in cfDNA and not in tissue DNA, or vice-versa. In neuroblastoma samples, no false-positives or false-negatives were identified for the detection of the prognostic marker MYCN amplification. Conclusion: In future prospective studies, CNA analysis on LQBs that are of sufficient quality can serve as a complementary assay for CNA analysis on tissue biopsies, as either cfDNA or tissue DNA can contain CNAs that cannot be identified in the other biomaterial.
- Published
- 2022