Adrenocortical Carcinoma Genomic Profile

Adrenocortical carcinoma (ACC) is a rare and highly aggressive cancer of the adrenal gland, with an incidence of 0.5–2 cases per million worldwide. It shows a bimodal age distribution, occurring in both children and adults, and presents with heterogeneous clinical behavior and variable symptoms. Although its etiology and prognosis remain unclear, early detection significantly reduces mortality. Advances in high-throughput genomic technologies have enabled genome-wide identification of disease-associated genes and variants, improving diagnosis, prognosis, and disease prediction. Despite representing a significant health burden in Saudi Arabia, ACC remains poorly studied, with no prior comprehensive investigations of its molecular and clinical characteristics in the Saudi population. This study aims to address this gap by conducting an integrated genomic and clinical characterization of ACC patients using next-generation sequencing. The focus is on identifying pathogenic variants in known ACC driver genes, including CTNNB1, TP53, CDKN2A, RB1, MEN1, ZNRF3, DAXX, TERT, and MED12. The specific objectives include:

1. Identification and characterization of novel genes and pathogenic variants associated with primary ACC using NGS.

2. Generation of comprehensive catalogues of genomic alterations, clinical presentations and pathological variables involved in the pathogenesis for all ACC cases at KFSH&RC, Riyadh, Saudi Arabia.

3. Identification of candidate genes and/or molecular biomarkers underline in ACC metastasis that can be used for prediction of diagnosis and prognosis.

4. Assessing ACC primary tumor evolution and their metastases (secondary ACC).

Expected outcomes: Through comprehensive genomic analysis, the study will generate a catalogue of causative variants and potential risk biomarkers that can support the development of future diagnostic and prognostic tests for ACC. Identifying disease-causing mutations specific to Saudi patients will assist clinicians in confirming diagnoses, stratifying patients, and guiding treatment decisions. Early detection enabled by these findings is expected to improve treatment success, enhance preoperative evaluation, and optimize healthcare and economic resource management. Additionally, the discovery of novel biomarkers and potential drug targets may offer opportunities for patentable innovations and improved clinical management of ACC.