Comparative analysis of whole-genome sequencing of tumor and cfDNA in a neuroblastoma patient: a case report
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 CNV profiling....
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2025.1569520/full |
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| author | Susanne Fransson Kleopatra Georgantzi Anna Djos Jennie Gaarder Johanna Svensson Vimala Anthonydhason Per Kogner Tommy Martinsson Ganesh Umapathy |
| author_facet | Susanne Fransson Kleopatra Georgantzi Anna Djos Jennie Gaarder Johanna Svensson Vimala Anthonydhason Per Kogner Tommy Martinsson Ganesh Umapathy |
| author_sort | Susanne Fransson |
| collection | DOAJ |
| description | 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 CNV profiling. We conducted whole-genome sequencing (WGS) of the circulating cell-free DNA (cfDNA) from a patient with NB and compared the WGS of the primary and relapsed tumor tissue. Our analysis revealed concordance between the somatic single nucleotide variants (SNVs), insertions and deletions (indels), and CNVs identified in the cfDNA and tumor WGS. Notably, WGS detected numerical chromosome imbalances, large and focal structural aberrations including amplifications in MYCN, CDK4, and MDM2, using low-input cfDNA. Furthermore, additional variants unique to the cfDNA, such as 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 patients with NB. This approach holds promise for improving prognostication and for guiding personalized treatment strategies in NB. |
| format | Article |
| id | doaj-art-afdf8e52f32044319639ce3ecc23e7b3 |
| institution | Kabale University |
| issn | 2234-943X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj-art-afdf8e52f32044319639ce3ecc23e7b32025-08-20T03:52:02ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-05-011510.3389/fonc.2025.15695201569520Comparative analysis of whole-genome sequencing of tumor and cfDNA in a neuroblastoma patient: a case reportSusanne Fransson0Kleopatra Georgantzi1Anna Djos2Jennie Gaarder3Johanna Svensson4Vimala Anthonydhason5Per Kogner6Tommy Martinsson7Ganesh Umapathy8Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenChildhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Pediatric Oncology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenSchool of Biomedical Sciences and Pharmacy, College of Health, The University of Newcastle, Newcastle, NSW, AustraliaChildhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, and Pediatric Oncology, Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenHigh-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 CNV profiling. We conducted whole-genome sequencing (WGS) of the circulating cell-free DNA (cfDNA) from a patient with NB and compared the WGS of the primary and relapsed tumor tissue. Our analysis revealed concordance between the somatic single nucleotide variants (SNVs), insertions and deletions (indels), and CNVs identified in the cfDNA and tumor WGS. Notably, WGS detected numerical chromosome imbalances, large and focal structural aberrations including amplifications in MYCN, CDK4, and MDM2, using low-input cfDNA. Furthermore, additional variants unique to the cfDNA, such as 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 patients with NB. This approach holds promise for improving prognostication and for guiding personalized treatment strategies in NB.https://www.frontiersin.org/articles/10.3389/fonc.2025.1569520/fullcirculating cell free DNA (cfDNA)whole genome sequencing (WGS)MET (c-MET)liquid biopsyneuroblastoma |
| spellingShingle | Susanne Fransson Kleopatra Georgantzi Anna Djos Jennie Gaarder Johanna Svensson Vimala Anthonydhason Per Kogner Tommy Martinsson Ganesh Umapathy Comparative analysis of whole-genome sequencing of tumor and cfDNA in a neuroblastoma patient: a case report Frontiers in Oncology circulating cell free DNA (cfDNA) whole genome sequencing (WGS) MET (c-MET) liquid biopsy neuroblastoma |
| title | Comparative analysis of whole-genome sequencing of tumor and cfDNA in a neuroblastoma patient: a case report |
| title_full | Comparative analysis of whole-genome sequencing of tumor and cfDNA in a neuroblastoma patient: a case report |
| title_fullStr | Comparative analysis of whole-genome sequencing of tumor and cfDNA in a neuroblastoma patient: a case report |
| title_full_unstemmed | Comparative analysis of whole-genome sequencing of tumor and cfDNA in a neuroblastoma patient: a case report |
| title_short | Comparative analysis of whole-genome sequencing of tumor and cfDNA in a neuroblastoma patient: a case report |
| title_sort | comparative analysis of whole genome sequencing of tumor and cfdna in a neuroblastoma patient a case report |
| topic | circulating cell free DNA (cfDNA) whole genome sequencing (WGS) MET (c-MET) liquid biopsy neuroblastoma |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2025.1569520/full |
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