Shallow Whole Genome Sequencing on Circulating Cell-Free DNA Allows Reliable Noninvasive Copy-Number Profiling in Neuroblastoma Patients.

Abstract

Purpose: Neuroblastoma (NB) is a heterogeneous disease characterized by distinct clinical features and by the presence of typical copy-number alterations (CNAs). Given the strong association of these CNA profiles with prognosis, analysis of the CNA profile at diagnosis is mandatory. Therefore, we tested whether the analysis of circulating cell-free DNA (cfDNA) present in plasma samples of patients with NB could offer a valuable alternative to primary tumor DNA for CNA profiling.Experimental Design: In 37 patients with NB, cfDNA analysis using shallow whole genome sequencing (sWGS) was compared with arrayCGH analysis of primary tumor tissue.Results: Comparison of CNA profiles on cfDNA showed highly concordant patterns, particularly in high-stage patients. Numerical chromosome imbalances as well as large and focal structural aberrations including MYCN and LIN28B amplification and ATRX deletion could be readily detected with sWGS using a low input of cfDNA.Conclusions: In conclusion, sWGS analysis on cfDNA offers a cost-effective, noninvasive, rapid, robust and sensitive alternative for tumor DNA copy-number profiling in most patients with NB. Clin Cancer Res; 23(20); 6305-14. ©2017 AACR.

• Authors: Nadine Van Roy, Malaïka Van Der Linden, Björn Menten, Annelies Dheedene, Charlotte Vandeputte, Jo Van Dorpe, Geneviève Laureys, Marleen Renard, Tom Sante, Tim Lammens, Bram De Wilde, Frank Speleman, Katleen De Preter
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 20 Pg. 6305-6314 (Oct 15 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28710315 (Publication Type: Journal Article)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Biomarkers, Tumor
• Circulating Tumor DNA

Topics

• Biomarkers, Tumor
• Child, Preschool
• Circulating Tumor DNA
• Comparative Genomic Hybridization
• DNA Copy Number Variations
• Genes, myc
• Humans
• Infant
• Liquid Biopsy
• Neoplasm Metastasis
• Neoplasm Staging
• Neuroblastoma (diagnosis, genetics)
• Whole Genome Sequencing