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Updated: May 29, 2025
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
ccfDNA analysis for the classification of adrenocortical adenomas
Mengjie Xu1,2, David S Tourigny3, Juliane Lippert4
1Department of Metabolism and Systems Science, College of Medicine and Health, University of Birmingham, Birmingham, UK.
Background:
Somatic alterations are commonly observed in adrenocortical adenomas including cortisol-producing (CPA) [overt Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS)], aldosterone-producing (APA), and non-functioning (NFAT) tumors. We tested whether somatic variants could be detected in circulating cell-free DNA (ccfDNA) from patients with adenomas and potentially contribute to management strategies.
Materials And Methods:
We investigated 44 patients (17 CPA-MACS, 9 CPA-CS, 12 APA, and 6 NFAT). 23 healthy subjects (HS) served as controls. ccfDNA was extracted from blood samples and quantified with fluorimeter. Tumor DNA (T-DNA) was isolated from paraffin embedded tissue in 17/44 cases. Matched ccfDNA/T-DNA were sequenced using a customized panel including 32 genes. Leucocyte DNA was used to filter out germline variants.
Results:
Patients with adenomas had higher total ccfDNA concentrations than HS [median 0.12 (IQR 0.05-0.19) vs. 0.05 (0.00-0.08) ng/µl, P < 0.001], with CPA-CS showing the highest ccfDNA levels [0.18 (0.05-0.47) ng/µl]. Within T-DNA, somatic variants were identified in 53% of adenomas: PRKACA in 2/7 CPA-CS, CTNNB1 in 3/5 CPA-MACS and 1/7 CPA-CS, KCNJ5 in 2/5 APA and CACNA1D in 1/5 APA. Somatic mutations were not detected in any of the investigated ccfDNA samples.
Conclusions:
Total ccfDNA concentrations are higher in patients with CPA-CS. Despite the presence of somatic variants in half of tumor samples, we did not detect any at ccfDNA level. Therefore, this approach appears ineffective for pre-operative detection of genetic alterations.
