Plasma ctDNA liquid biopsy of IDH1, TERTp, and EGFRvIII mutations in glioma.

BACKGROUND

Circulating tumor DNA has emerging clinical applications in several cancers; however, previous studies have shown low sensitivity in glioma. We investigated if 3 key glioma gene mutations , , and could be reliably detected in plasma by droplet digital polymerase chain reaction (ddPCR) thereby demonstrating the potential of this technique for glioma liquid biopsy.

METHODS

We analyzed 110 glioma patients from our biobank with a total of 359 plasma samples (median 4 samples per patient). DNA was isolated from plasma and analyzed for , , and mutations using ddPCR.

RESULTS

Total cfDNA was significantly associated with tumor grade, tumor volume, and both overall and progression-free survival for all gliomas as well as the grade 4 glioblastoma subgroup, but was not reliably associated with changes in tumor volume/progression during the patients' postoperative time course. mutation was detected with 84% overall sensitivity across all plasma samples and 77% in the preoperative samples alone; however, mutation plasma levels were not associated with tumor progression or survival. plasma levels were not associated with pre- or postsurgery progression or survival. The mutation was detected in the plasma ctDNA in 88% but the variant in only 49% of samples. The mutation was detected in plasma in 5 out of 7 patients (71%) with tissue mutations in tumor tissue.

CONCLUSIONS

Plasma ctDNA mutations detected with ddPCR provide excellent diagnostic sensitivity for , , and mutations in glioma patients. Total cfDNA may also assist with prognostic information. Further studies are needed to validate these findings and the clinical role of ctDNA in glioma.