The identification of circulating tumour DNA using MassARRAY technology in non-small-cell lung cancer (NSCLC)

Abstract

Objectives: Attaining tumour material from lung cancer patients can be challenging with limited sample availability. Therefore, non-invasive means of assessing tumour material is becoming increasingly more important. Circulating tumour DNA (ctDNA), extracted from a blood sample is appealing for the patient, and can be performed serially over the course of treatment.

Materials and methods: Here, we describe an approach for profiling the blood samples of 103 NSCLC patients for 73 variants in ctDNA across a panel of actionable lung cancer mutations using the UltraSEEK lung Panel (Agena Biosciences).

Results: Our cross-sectional study showed tumour and blood concordance in the detection of KRAS mutations (G12C, G12D, G12A/V, G12R, G12RC, Q61H) in 17/27 (63%), EGFR mutations (e746_a750del, e747_A750, T790M, L861Q) in 16/20 (80%) with additional PIK3CA_p545K mutations across both cohorts. In patients without reported tumour mutations, 11/56 (19.6%) presented with plasma mutations across EGFR, KRAS and PIK3CA. Where ctDNA mutations were measured longitudinally (n = 4 patients), the individual mutations mirrored the response to therapy/progression of disease.

Conclusion: Whilst preliminary, this study demonstrates the utility of detecting clinically actionable mutations in the blood samples of NSCLC patients at the time of presentation, and over the course of therapy.

Keywords: Circulating tumour DNA; EGFR; KRAS; Lung cancer; Mutations; Ultraseek.