期刊
EUROPEAN JOURNAL OF CANCER
卷 160, 期 -, 页码 12-23出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2021.09.022
关键词
Liquid biopsy; cfDNA; Biomarker; Copy number aberrations; Shallow whole-genome sequencing
类别
资金
- Research Foundation Flanders (FWO) - Kom op tegen Kanker (Stand Up to Cancer) [11R8616N, 1S90621N, 11B3718N]
- Flemish Cancer Society [EvdS 00000000074000000157]
- vzw Kinderkankerfonds e a non-profit childhood cancer foundation
- VIB Grand Challenges Program
- Belgian Society of Paediatric Haematology Oncology
- Annenberg Foundation
- Association Hubert Gouin Enfance et Cancer
- SiRIC programme
- Koningin Wilhelmina Fund
- [8352/TRS-2018-00000715]
There is a good agreement between DNA copy number alterations (CNAs) in tissue DNA and circulating cell-free DNA (cfDNA) obtained from liquid biopsies. The quality of cfDNA sample can affect the concordance between tissue DNA and cfDNA CNAs. Liquid biopsies can provide complementary analysis to tissue biopsies, as both cfDNA and tissue DNA can contain CNAs that cannot be identified in the other biomaterial.
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 Z 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) and high molecular weight DNA (>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. 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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