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The potential of liquid biopsy for detection of the KIAA1549-BRAF fusion in circulating tumor DNA from children with pilocytic astrocytoma.
Krynina, Olha; de Ståhl, Teresita Díaz; Jylhä, Cecilia; Arthur, Cecilia; Giraud, Geraldine; Nyman, Per; Fritzberg, Anders; Sandgren, Johanna; Tham, Emma; Sandvik, Ulrika.
Affiliation
  • Krynina O; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • de Ståhl TD; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
  • Jylhä C; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Arthur C; Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden.
  • Giraud G; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • Nyman P; Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden.
  • Fritzberg A; Department of Immunology, Genetic and Pathology, Neuro-oncology, and Neurodegeneration Program Rudbeck Laboratory, Uppsala, Sweden.
  • Sandgren J; Department of Women and Children's Health, Akademiska University Hospital, Uppsala, Sweden.
  • Tham E; Department of Health, Crown Princess Victoria Children´s Hospital, Linköping University Hospital, Linköping, Sweden.
  • Sandvik U; Department of Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
Neurooncol Adv ; 6(1): vdae008, 2024.
Article in En | MEDLINE | ID: mdl-38371226
ABSTRACT

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 KIAA1549BRAF 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 KIAA1549BRAF 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.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Neurooncol Adv Year: 2024 Document type: Article Affiliation country: Sweden Country of publication: United kingdom

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Neurooncol Adv Year: 2024 Document type: Article Affiliation country: Sweden Country of publication: United kingdom