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Updated: Dec 13, 2025
A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
Molecular genomic profiling of adrenocortical cancers in clinical practice
Sourat Darabi1, David R Braxton1, Burton L Eisenberg2
1Hoag Family Cancer Institute, Precision Medicine Program, Newport Beach, CA.
Background:
At presentation, 21% to 49% of patients with adrenocortical cancer have metastases. Standard chemotherapy has a 23% response rate. We assessed whether next generation sequencing could elucidate additional treatment options in refractory adrenocortical cancer.
Methods:
Retrospective analysis using a commercial, 592-gene DNA-based panel was performed of next generation sequencing data from 94 adrenocortical cancer tumors profiled for clinical care. We compared our data to the adrenocortical cancer database of The Cancer Genome Atlas containing survival data. We evaluated mutations, indels, amplifications, tumor mutation burden, microsatellite instability, and programmed death-ligand 1 protein expression.
Results:
Our cohort included 54 primary neoplasms and 40 metastatic lesions. The most frequently mutated genes were TP53 (36%) and CTNNB1 (19%). Low prevalence mutations were noted in 37 genes including DNA damage repair genes in 15 samples. High tumor mutation burden was seen in 3 patients, and programmed death-ligand 1 was positive in 12. Potential targets to Food and Drug Administration-approved drugs were seen in 16% of cases.
Conclusion:
DNA sequencing panel tests may identify therapeutic options for some patients with adrenocortical cancer. TP53 and mutations were associated with an adverse outcome. An expanded repertoire of drugs and, perhaps, more expansive multi-omic sequencing are needed to advance the treatment of adrenocortical cancer.
Insights
Next-generation sequencing identified potential new treatments for adrenocortical cancer, a rare disease. TP53 mutations were linked to worse outcomes, highlighting the need for advanced genomic analysis and novel therapies.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Adrenocortical cancer frequently presents with metastases (21-49%) and shows limited response to standard chemotherapy (23%).
- Identifying novel therapeutic strategies is crucial for improving outcomes in refractory adrenocortical cancer.
- Next-generation sequencing (NGS) offers a potential avenue for discovering new treatment options.
Purpose of the Study:
- To evaluate the utility of NGS in identifying actionable targets for refractory adrenocortical cancer.
- To compare genomic profiles of adrenocortical tumors with The Cancer Genome Atlas (TCGA) database.
- To investigate the prevalence of specific mutations, tumor mutational burden, and PD-L1 expression.
Main Methods:
- Retrospective analysis of NGS data from 94 adrenocortical cancer tumors using a 592-gene DNA panel.
- Comparison with TCGA adrenocortical cancer database for survival data correlation.
- Assessment of mutations, indels, amplifications, tumor mutation burden (TMB), microsatellite instability (MSI), and programmed death-ligand 1 (PD-L1) expression.
Main Results:
- The cohort comprised 54 primary and 40 metastatic adrenocortical neoplasms.
- TP53 (36%) and CTNNB1 (19%) were the most frequently mutated genes.
- Actionable targets for FDA-approved drugs were identified in 16% of cases; 12% showed PD-L1 positivity.
Conclusions:
- NGS panel testing can reveal potential therapeutic targets for select adrenocortical cancer patients.
- TP53 mutations are associated with poorer prognosis in adrenocortical cancer.
- Advancing adrenocortical cancer treatment requires a broader range of drugs and comprehensive multi-omic sequencing approaches.
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