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A Novel Method: Super-selective Adrenal Venous Sampling
Published on: September 15, 2017
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Targeted Mutational Analysis of Cortisol-Producing Adenomas
Juilee Rege1, Jessie Hoxie1, Chia-Jen Liu2
1Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
The Journal of Clinical Endocrinology and Metabolism
|September 17, 2021
Summary
Somatic mutations were found in 71.8% of cortisol-producing adenomas (CPAs). Overt Cushing syndrome (OCS) CPAs showed different genetic changes than mild autonomous cortisol excess (MACE) CPAs.
Area of Science:
- Endocrinology
- Oncology
- Genetics
Background:
- Somatic gene mutations are found in about half of cortisol-producing adenomas (CPAs).
- Known affected genes include PRKACA, GNAS, PRKAR1A, and CTNNB1.
Purpose of the Study:
- To determine the prevalence of somatic mutations in CPAs from patients with overt Cushing syndrome (OCS) and mild autonomous cortisol excess (MACE).
- To utilize an immunohistochemistry (IHC)-guided targeted amplicon sequencing approach on formalin-fixed paraffin-embedded (FFPE) tissue.
Main Methods:
- Analyzed FFPE adrenal tissue from 77 patients (32 OCS, 45 MACE).
- Used IHC for CYP17A1 and HSD3B2 to identify 78 CPAs.
- Performed targeted amplicon sequencing on isolated genomic DNA from FFPE CPAs to identify somatic mutations.
Main Results:
- Somatic mutations were identified in 71.8% (56/78) of CPAs.
- PRKACA mutations were most common in OCS CPAs (43.8%), while CTNNB1 mutations predominated in MACE CPAs (56.5%).
- GNAS mutations were more frequent in MACE CPAs (71.4%); no PRKAR1A mutations were found. One new PRKACA mutation was identified.
Conclusions:
- An IHC-guided, gene-targeted sequencing approach on FFPE tissue successfully identified somatic mutations in 71.8% of CPAs.
- Distinct somatic mutation profiles were observed between OCS CPAs and MACE CPAs.
