G. Smith et al. (2021) European Congress of Endocrinology: Endocrine Abstracts, 73.
Adrenocortical Carcinoma (ACC) is a rare aggressive cancer with a heterogeneous behaviour. Disease surveillance relies on frequent imaging, which has limited sensitivity and results in significant radiation exposure. Aim of the study was to investigate the role of circulating cell-free DNA (ccfDNA) as a biomarker for prognostication and disease monitoring in ACC.
ccfDNA was extracted from 1–4 ml EDTA-plasma using the Nonacus Cell3 Xtract or the Qiagen QIAamp MinElute ccfDNA kit and quantified by fluorimetry. The experimental cohort included 60 patients with ACC (22M/36F, 52 ± 15 yrs): 22 primary tumours (ACC-P) and 38 disease recurrences (ACC-R). Twenty-three patients with adrenocortical adenomas (ACA, 8M/15F, 55 ± 17 yrs) and 19 healthy subjects (9M/10F, 37 ± 9 yrs) served as controls. Targeted next generation sequencing was performed on 23 ccfDNA samples (8 ACC-P, 11 ACC-R, 4 ACA) using a customised panel of 30 ACC-specific genes (Cell3 Target Nonacus) and Illumina NextSeq500 Sequencer. Leucocyte DNA was sequenced to discriminate germline from somatic variants. Sequencing data from corresponding tumour DNA (tDNA) were available for comparison in 13/19 ACC.
ccfDNA concentrations correlated with tumour burden in patients with ACC and may have utility in predicting disease recurrence. Targeted ccfDNA sequencing detected ACC-specific mutations in ~30% of ACC. Serial ccfDNA quantitative and genomic analysis may represent an efficient, non-invasive tool complementary to imaging to improve the disease surveillance in ACC. This will be investigated in a large cohort of operated patients.