Comparative Analysis of Whole Genome Sequencing of Tumor and cfDNA in a Neuroblastoma Patient: A Case Study

Susanne Fransson ¹ Kleopatra Georgantzi ² Anna Djos ¹ Jennie Gaarder ¹ Johanna Svensson ¹ Vimala Anthonydhason ³ Per Kogner ² Tommy Martinsson ¹ Ganesh Umapathy ^1*

• ¹ Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
• ² Karolinska University Hospital, Stockholm, Sweden
• ³ The University of Newcastle, Callaghan, New South Wales, Australia

High-risk neuroblastoma (NB) poses significant challenges in pediatric oncology due to its resistance to conventional therapies, leading to relapse and poor prognosis.Copy number variations (CNVs) are strong prognostic factors in NB, prompting exploration into alternative methods for profiling CNVs. We conducted wholegenome sequencing (WGS) of circulating cell-free DNA (cfDNA) from a NB patient and compared it WGS of primary and relapsed tumor tissue. Our analysis revealed concordance between somatic single nucleotide variants (SNVs), insertions and deletions (Indels), and CNVs identified in cfDNA and tumor WGS. Notably, WGS detected numerical chromosome imbalances, large and focal structural aberrations including MYCN, CDK4, and MDM2 amplifications, using low input cfDNA.Furthermore, additional variants unique to the cfDNA, including the rare MET (p.R970C) variant, were identified, possibly representing sub-clonal populations or variants present at metastatic sites. In conclusion, WGS analysis of cfDNA offers a noninvasive, cost-effective, rapid, and sensitive alternative for CNV profiling in NB patients. This approach holds promise for improving prognostication and guiding personalized treatment strategies in NB.