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Updated: May 20, 2025
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Two-dimensional Gel Electrophoresis Coupled with Mass Spectrometry Methods for an Analysis of Human Pituitary Adenoma Tissue Proteome
Published on: April 2, 2018
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Genetic Profiling of Synchronous Pituitary Corticotroph Adenomas
Dongyun Zhang1, Karen Tsai1, Cristian Santana1
1University of California.
Research Square
|May 19, 2025
Summary
Multiple pituitary adenomas are rare. This study identified distinct genetic variants, GPR162 and USP8, in two separate corticotroph tumors, suggesting unique molecular drivers for each tumor.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Multiple pituitary adenomas are uncommon, accounting for 1.6-3.3% of corticotroph tumors.
- Understanding the molecular basis of distinct, co-occurring pituitary adenomas is crucial for diagnosis and treatment.
Purpose of the Study:
- To investigate the molecular pathogenesis of two distinct corticotroph adenomas in a single patient.
- To identify and functionally characterize genetic variants driving the development of multiple pituitary tumors.
Main Methods:
- Whole exome sequencing (WES) was performed on two separate corticotroph adenomas and a blood sample.
- Functional assays assessed the impact of identified variants on pro-opio-melanocortin (POMC) transcription and cell proliferation in murine models.
Main Results:
- WES revealed a loss-of-function GPR162 (R218*) variant in one tumor and a novel USP8 (P681Q) variant in the other.
- GPR162 (R218*) showed reduced POMC transcription inhibition, while USP8 (P681Q) increased POMC transcription, similar to known variants.
- A germline CYP21A2 variant was identified, with absent CYP21A2 transcript and protein in both tumors.
Conclusions:
- Distinct somatic variants in GPR162 and USP8 drive the development of individual corticotroph tumors.
- A germline CYP21A2 variant may predispose to corticotroph tumor development by increasing cell stimulation, facilitating somatic mutations.
