Dynamics of cell-free DNA in predicting response in adult diffuse glioma on chemoradiotherapy

Cancer Genet. 2022 Nov:268-269:55-63. doi: 10.1016/j.cancergen.2022.09.006. Epub 2022 Sep 19.

Abstract

Background: Adult diffuse glioma (ADG) is a heterogeneous primary brain tumor with a variable prognosis and treatment response. Tissue biomarkers and molecular genetic profiling form an integral part of diagnosis and prognostication. However, obtaining tissue in inoperable locations and diagnosis of recurrence can be an issue. Cell-free DNA (cfDNA) may help to meet these challenges in the management of ADG.

Objectives: The study aimed to serially quantify cfDNA in ADG on chemoradiation and to correlate mutational profiling of the cfDNA with biopsy.

Material and methods: The study group comprised of histopathological confirmed ADG (n = 50), including grade II, III and IV glioma, and controls (n = 25). Serum cfDNA was extracted using ChargeSwitch gDNA 1 mL Serum Kit (Invitrogen, USA) and quantified using SYBR based quantitative polymerase chain reaction (qPCR). Next-generation sequencing (NGS) was performed in 07 pre-operative and 05 post-operative cfDNA and tumor biopsy DNA on an Ion personal genome machine (IonPGM) with an in-house designed NGS panel (including TP53, ATRX, and IDH1 and IDH2).

Results: In patients with ADG, the pre-radiotherapy cfDNA level was significantly higher (Median; 113.46 ng/mL) than normal controls (Median; 74.37 ng/mL), (p = 0.048). Non-responders had significantly higher cfDNA levels (Median; 184.4 ng/mL), than responders (Median; 68.12 ng/mL), (p = 0.023). TP53 gene mutation was most common in both pre-operative and post-operative cfDNA samples.

Conclusion: Pre-radiotherapy cfDNA levels are associated with clinical outcomes independent of other prognostic factors. Targeted NGS in pre-operative cfDNA matches the results of IHC analysis with high concordance, and it may be helpful in inoperable cases or ADG recurrence.

Keywords: Adult diffuse glioma; Cell-free DNA; Liquid biopsy; Next generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers, Tumor / genetics
  • Cell-Free Nucleic Acids* / genetics
  • Chemoradiotherapy
  • DNA, Neoplasm
  • Glioma* / diagnosis
  • Glioma* / genetics
  • Glioma* / therapy
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Mutation

Substances

  • Cell-Free Nucleic Acids
  • DNA, Neoplasm
  • Biomarkers, Tumor