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

Published:September 18, 2022DOI:https://doi.org/10.1016/j.cancergen.2022.09.006

      Highlights

      • Adult diffuse glioma is a heterogeneous brain tumor with a variable prognosis and treatment response.
      • Cell-free DNA (cfDNA) may help to meet challenges in the management of inoperable and recurrent ADG.
      • cfDNA levels are associated with clinical outcomes and independent prognostic factors
      • Targeted NGS in pre-operative cfDNA matches the results of IHC analysis with high concordance,
      • Mutational analysis in cfDNA samples might be a surrogate for tissue

      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

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