Detection of Somatic Mutations in Circulating Tumor DNA of Patients with Operable Lung Cancer—A Pilot Study

Objectives: Occurrence of metastases is usually fatal in patients with bronchial carcinoma since diagnosis is usually too late. Further, operable patients relapse in 30% of the cases. Therefore, early screening by minimally invasive methods for risk of metastases and recurrence is an urgent medical need. Droplet digital PCR (ddPCR) is an effective means of specifically and sensitively detecting circulating tumor DNA in plasma and revealing possible indications of metastases.

Methods: In 22 patients with locally advanced bronchial carcinoma in operable stages I to IIIA, blood samples were taken prior to surgery. Genomic DNA from frozen tumor tissue were extracted and analyzed for mutational status of 17 genes using a custom next-generation sequencing (NGS) panel. Further, ddPCR was performed on plasma samples.

Results: In 21 of 22 (95%) of the analyzed bronchial carcinoma tumor tissues at least one somatic mutation was detected with NGS. All patients were treated for non-small cell lung cancer. Ten of 22 (45%) patients had squamous cell carcinoma. DdPCR was capable of detecting mutations in ctDNA in 6 of 22 patients (27%). Three of 6 patients with positive detection in plasma were in stage IB.

Conclusion: These are preliminary results showing that ddPCR is feasible in detection of somatic mutations in circulating cell-free DNA in patients with early stage bronchial carcinoma. Further, genetic data will be correlated with the patients’ outcome.

No conflict of interest has been declared by the author(s).