SFEBES2021 Oral Communications Adrenal and Cardiovascular (6 abstracts)
Circulating cell-free DNA-based biomarkers as a tool for disease surveillance in adrenocortical carcinoma
Gabrielle Smith 1 , Juliane Lippert 2 , Barbara Altieri 2 , Yasir Elhassan 1 , Laura Landwehr 2 , Alessandro Prete 1 , Silke Appenzeller 3 , Vasileios Chortis 1 , Sonja Steinhauer 2 , Miriam Asia 4 , Robert Sutcliffe 4 , Wiebke Arlt 1 , Martin Fassnacht 2 & Cristina Ronchi 1,2
1Institute of Metabolism and System Research, Birmingham, United Kingdom; 2University Hospital of Wuerzburg, Wuerzburg, Germany; 3University of Wuerzburg, Wuerzburg, Germany; 4Queen Elizabeth Hospital, Birmingham, United Kingdom
Adrenocortical carcinoma (ACC) is a rare aggressive cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. Here we investigated the role of circulating cell-free DNA (ccfDNA) in ACC monitoring. We extracted ccfDNA from 1-4 ml EDTA-plasma using the Nonacus Cell3TMXtract or the Qiagen QIAamp MinElute kit and quantified by fluorimeter. We investigated 63 patients with ACC (25M/38F, 52±15yrs; 25 primary tumours [ACC-P] and 38 recurrences [ACC-R]); while 26 patients with adrenocortical adenomas (8M/18F, 55±17yrs) and 19 healthy subjects (9M/10F, 37±9yrs) served as controls. Targeted next generation sequencing (Illumina NextSeq500) was performed on 34 ccfDNA samples (12 ACC-P, 14 ACC-R, 8 adenomas) using a customised panel of 30 ACC-specific genes (Cell3TMTarget Nonacus). Leucocyte DNA was sequenced to discriminate germline from somatic variants. Sequencing data from matched tumour-DNA were available for 13 ACC. ACC-P had the highest ccfDNA concentrations (0.99±1.46 ng/µl) compared to ACC-R (0.23±0.22 ng/µl, P < 0.05), adenomas (0.17±0.13 ng/µl, P < 0.005) and healthy subjects (0.11±0.07 ng/µl, P < 0.005). In ACC, ccfDNA levels correlated with the tumour burden, i.e. size of tumour manifestations plus number of metastasis (P < 0.001, R=0.57). In ACC-P, ccfDNA concentrations correlated with ENSAT stage (P < 0.05) and were negatively associated with recurrence-free survival (n = 14, P=0.039, HR 7.54, 95%CI 1.2-47.5). Among sequenced ccfDNA samples, 6 ACC-P (50%) and 3 ACC-R (21%), but no adenomas, showed somatic mutations in at least one ACC driver gene (4 CTNNB1, 4 TP53, 3 ZNRF3, 2 MEN1, 1 DAXX, 1 RB1). CcfDNA sequencing matched with tumour-DNA results in 69% of cases. In conclusion, ccfDNA concentrations correlate with tumour burden and may predict disease recurrence in patients with ACC. Targeted ccfDNA sequencing detected ACC-specific mutations in half of the patients. Thus, ccfDNA-based liquid biopsy may represent a promising, non-invasive tool complementing imaging in disease surveillance.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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