Plasma circulating tumor DNA profiling in patients with chemo-refractory germ cell tumors.

Objectives: Molecular analysis of tumor tissues has been extensively analyzed in germ cell tumors. However, genetic analysis of plasma circulating tumor DNA has been limited. Our objective was to analyze genetic alterations in circulating tumor DNA as well as its impact on prognosis in patients with chemo-refractory germ cell tumors.

Methods: We included 13 patients with chemo-refractory germ cell tumors who relapsed after second-line or higher previous chemotherapy and performed targeted sequencing of plasma cell-free DNA using an AVENIO Expanded kit.

Results: Tumor-specific genetic alterations were identified in all patients. The most frequently mutated gene was TP53 (53.4%), followed by PTEN (23.1%), GNAS (15.4%) and MTOR (15.4%). Moreover, EGFR amplification (38.5%) and MET amplification (15.4%) were also identified. We defined two or more single nucleotide variants detected in plasma cell-free DNA as circulating tumor DNA-positive. Kaplan-Meier analysis revealed that overall survival was significantly shorter in circulating tumor DNA-positive patients than circulating tumor DNA negative-patients (median overall survival 3.13 vs. 8.73 months; p = 0.042).

Conclusion: Analysis of plasma circulating tumor DNA could detect genetic alterations in patients with chemo-refractory GCT. Moreover, detectable circulating tumor DNA in plasma was associated with poor prognosis in those patients. These results suggest that liquid biopsy using analysis of plasma circulating tumor DNA may be clinically useful for germ cell tumor patients.