Clinical utility of plasma cell-free DNA (cfDNA) in diffuse gliomas for the detection of IDH1 R132H mutation

Pathol Res Pract. 2024 Nov:263:155571. doi: 10.1016/j.prp.2024.155571. Epub 2024 Sep 14.

Abstract

Liquid biopsy for CNS tumors is in its nascent phase, hindered by the low levels of circulating tumor DNA (ctDNA). Overcoming this challenge requires highly sensitive molecular techniques. DD-PCR emerges as a standout technique due to its ability to identify rare mutations, copy number variations, and circulating nucleic acids, making it one of the best methods for identifying somatic mutations in cell-free DNA (cfDNA). Despite promising results from various studies demonstrating the feasibility of obtaining informative ctDNA profiles from liquid biopsy samples, challenges persist, including the need to standardize sample collection, storage, and processing methods, define clear assay positivity thresholds, and address the overall low assay sensitivity. Our two-phase study began by assessing DD-PCR efficacy in FFPE tissues, revealing robust concordance with immunohistochemistry. In Phase 1 (85 cases), DD-PCR on FFPE tissues demonstrated 100 % sensitivity and specificity for IDH1 R132H mutations. In Phase 2 (100 cases), analysis extended to cfDNA, maintaining high specificity (100 %) with moderate sensitivity (44.2 %). Overall concordance with immunohistochemistry was 61 %, highlighting liquid biopsy's potential in glioma management. The findings emphasized DD-PCR's clinical utility in both tissue and liquid biopsy, underscoring its role in early detection, diagnosis, and therapeutic monitoring of diffuse gliomas.

Keywords: Cell free DNA; Clinical utility; Digital Droplet PCR; Isocitrate Dehydrogenase 1; Non-invasive.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor* / blood
  • Biomarkers, Tumor* / genetics
  • Brain Neoplasms* / blood
  • Brain Neoplasms* / diagnosis
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Cell-Free Nucleic Acids / blood
  • Cell-Free Nucleic Acids / genetics
  • Circulating Tumor DNA / analysis
  • Circulating Tumor DNA / blood
  • Circulating Tumor DNA / genetics
  • Female
  • Glioma* / blood
  • Glioma* / diagnosis
  • Glioma* / genetics
  • Glioma* / pathology
  • Humans
  • Isocitrate Dehydrogenase* / genetics
  • Liquid Biopsy / methods
  • Male
  • Middle Aged
  • Mutation*
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • Cell-Free Nucleic Acids