Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The potential of liquid biopsy for detection of the KIAA1549-BRAF fusion in circulating tumor DNA from children with pilocytic astrocytoma
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden..
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Genet & Genom, Stockholm, Sweden..
Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp, Clin Genet & Genom, Stockholm, Sweden..
Show others and affiliations
2024 (English)In: Neuro-Oncology Advances, E-ISSN 2632-2498, Vol. 6, no 1, article id vdae008Article in journal (Refereed) Published
Abstract [en]

Background

Low-grade gliomas (LGGs) represent children’s most prevalent central nervous system tumor, necessitating molecular profiling to diagnose and determine the most suitable treatment. Developing highly sensitive screening techniques for liquid biopsy samples is particularly beneficial, as it enables the early detection and molecular characterization of tumors with minimally invasive samples.

Methods

We examined CSF and plasma samples from patients with pilocytic astrocytoma (PA) using custom multiplexed droplet digital polymerase chain reaction (ddPCR) assays based on whole genome sequencing data. These assays included a screening test to analyze BRAF duplication and a targeted assay for the detection of patient-specific KIAA1549::BRAF fusion junction sequences or single nucleotide variants.

Results

Our findings revealed that 5 out of 13 individual cerebrospinal fluid (CSF) samples tested positive for circulating tumor DNA (ctDNA). Among these cases, 3 exhibited the KIAA1549::BRAF fusion, which was detected through copy number variation (CNV) analysis (n = 1) or a fusion-specific probe (n = 2), while 1 case each displayed the BRAF V600E mutation and the FGFR1 N577K mutation. Additionally, a quantitative analysis of cell-free DNA (cfDNA) concentrations in PA CSF samples showed that most cases had low cfDNA levels, below the limit of detection of our assay (<1.9 ng).

Conclusions

While CNV analysis of CSF samples from LGGs still has some limitations, it has the potential to serve as a valuable complementary tool. Furthermore, it can also be multiplexed with other aberrations, for example, to the BRAF V600 test, to provide important insights into the molecular characteristics of LGGs.

Place, publisher, year, edition, pages
Oxford University Press, 2024. Vol. 6, no 1, article id vdae008
Keywords [en]
cerebrospinal fluid, cfDNA, ddPCR, KIAA1549::BRAF, pilocytic astrocytoma
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-524335DOI: 10.1093/noajnl/vdae008ISI: 001163714900001PubMedID: 38371226OAI: oai:DiVA.org:uu-524335DiVA, id: diva2:1842027
Funder
Knut and Alice Wallenberg FoundationSwedish Research CouncilSwedish Childhood Cancer Foundation, KP2021-0017Swedish Childhood Cancer Foundation, TJ2021-0125Swedish Cancer Society, 22 2451Region Stockholm, FoUI-961732Region Stockholm, FoUI-973659Available from: 2024-03-01 Created: 2024-03-01 Last updated: 2024-03-01Bibliographically approved

Open Access in DiVA

fulltext(4148 kB)51 downloads
File information
File name FULLTEXT01.pdfFile size 4148 kBChecksum SHA-512
852eb6c8f8f33613e7a7a33c8cfff362e0ce494a151eb321ec081c879e36d441f75cc3f80df305ccd448b67d798ee4745cca533df94a3c0f817340f01d3951fe
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Authority records

Giraud, Geraldine

Search in DiVA

By author/editor
Giraud, Geraldine
By organisation
Science for Life Laboratory, SciLifeLabNeurooncology and neurodegeneration
In the same journal
Neuro-Oncology Advances
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 51 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 174 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf