ECEESPE2025 Rapid Communications Rapid Communications 1: Adrenal and Cardiovascular Endocrinology (5 abstracts)
Integrated liquid biopsy approach as disease monitoring tool in adrenocortical carcinoma: a preliminary study
David S. Tourigny 1 , Lorenzo Tucci 2,3 , Balqees Shabaan 2 , Meng Jie Xu 2,4 , Yasir Elhassan 2,5 , Kassiani Skordilis 5 , Miriam Felicitas Asia 5 , Alessandro Prete 2,6 , Ana Crastin 2 , Ezra Leander Onesimu 2 , Angela Taylor 2 , Vasileios Chortis 2 & Cristina L Ronchi 2
1University of Birmingham, School of Mathematics, Birmingham, United Kingdom; 2University of Birmingham, Department of Metabolism and Systems Science, Birmingham, United Kingdom; 3Alma Mater Studiorum University of Bologna, Bologna, Italy; 4Taihe Hospital, Hubei University of Medicine, Shiyan, China; 5Queen Elizabeth Hospital Birmingham NHS Trust, Department of Endocrinology, Birmingham, United Kingdom; 6University of Birmingham, NIHR Birmingham Biomedical Research Centre, Birmingham, United Kingdom
JOINT895
Background: Adrenocortical carcinoma (ACC) is a rare cancer with heterogeneous clinical outcome. Close disease monitoring is essential but relies on radiological imaging that comes with significant radiation exposure. Circulating cell-free DNA (ccfDNA) can contain tumour-derived somatic variants, representing a non-invasive tool for cancer monitoring. Similarly, tumour-derived steroid hormone metabolites can be detected in urine from patients with ACC and may provide an additional post-operative surveillance tool.
Aim: Evaluate the role of combined ccfDNA sequencing and urine steroid metabolomics (USM) to monitor disease recurrence in ACC.
Methods: We investigated 6 patients (1M/5F, median age 37.5yrs) with histologically confirmed ACC. Plasma and 24 h urine samples were collected before primary tumour resection (baseline), early post-operatively (28-42 days) and on 3-monthly follow-ups. ccfDNA and germline DNA (gDNA) were isolated with commercially available kits. Tumour DNA (tDNA) was isolated from paraffin-embedded tissue. ccfDNA/gDNA/tDNA were sequenced using a customized ACC-specific panel and by shallow (0.1×) whole genome sequencing (sWGS). Genetic alterations (including gene variants and copy number variations, CNV) were called following standard bioinformatic protocols. gDNA was used to discriminate somatic variants. 32 distinct adrenocortical steroid metabolites were quantified using gas chromatography/mass spectrometry and a previously developed generalised matrix learning vector quantisation algorithm was used to detect the presence of ACC.
Results: at tDNA level, 3/6 cases (50%) presented point mutations while all 6 cases (100%) had an altered CNV pattern at sWGS. tDNA-derived somatic alterations were detected in baseline ccfDNA from 4/6 patients (71%). USM demonstrated steroid profiles for ACC in 5/5 patients at baseline. Three patients developed radiological recurrence at 3 or 6 months, which coincided with detection of somatic alterations in follow-up ccfDNA samples in 2/3 cases (67%). In one case, sWGS gave a clear signal for recurrence that would otherwise be missed by targeted sequencing alone. USM detected ACC-diagnostic steroids at recurrence in all cases with available urine samples, one 3 months before radiological evidence of relapse. The other three patients remain tumour free at 2-year follow up. One case presented somatic alterations at baseline tDNA/ccfDNA that disappeared in follow-up ccfDNA. USM reliably showed no evidence of ACC-diagnostic steroids in both cases with available samples during the entire follow up.
Conclusion: Integrating molecular signatures from ccfDNA and USM could complement standard radiological surveillance in monitoring of patients with ACC. sWGS seems to have an additional value beyond targeted sequencing alone. Validation in a larger cohort is required to confirm our promising findings.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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