Evidence map›Paper›PMID 40544420›Full record

ArticlePituitary2025

Genetic profiling of synchronous pituitary corticotroph adenomas.

Dongyun Zhang, Karen Tsai, Cristian Santana, Keanu Javaherian, Matthew Lee, Marvin Bergsneider, Won Kim, Marilene B Wang, Harry V Vinters, Weihong Yan and 1 more

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Pituitary, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Dongyun ZhangDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
Karen TsaiDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
Cristian SantanaDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
Keanu JavaherianDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
Matthew LeeDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
Marvin BergsneiderDepartments of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, USA.
Won KimDepartments of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, USA.
Marilene B WangDepartments of Head and Neck Surgery, David Geffen School of Medicine, University of California, Los Angeles, USA.
Harry V VintersDepartments of Pathology and Lab Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
Weihong YanDepartments of Chemistry and Biochemistry, David Geffen School of Medicine, University of California, Los Angeles, USA.
Anthony P HeaneyDepartments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA. aheaney@mednet.ucla.edu.ORCID http://orcid.org/0000-0003-3865-0810

Funding

UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Development of 3-dimensional human pituitary corticotroph tumor cultures as a preclinical model for drug discoveryR01CA251930 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HEANEY, ANTHONY P · 2021 to 2025
$1.8M
NCI NIH HHS P50 CA211015NCI NIH HHS P50CA211015NCI NIH HHS R01 CA251930NCI NIH HHS R01CA251930
6 · The paper itself

Abstract

purposeDouble or multiple pituitary adenomas account for only 1.6-3.3% of all corticotroph tumors. We sought to better understand the underlying molecular pathogenesis of two distinct corticotroph adenomas in a 43-year-old female.

methodsTwo histopathologically confirmed corticotroph adenomas were submitted for whole-exome sequencing along with a matched blood sample. The functional effects of identified variants of uncertain significance on corticotroph tumor pro-opiomelanocortin transcription and proliferation were characterized.

resultsWES demonstrated a loss-of-function variant in the G-protein coupled receptor 162 [GPR162 (R218*)] in the right corticotroph tumor, and a novel missense variant in ubiquitin specific peptidase 8 [USP8 (P681Q)] in the left tumor. Compared to wild-type GPR162 which potently suppressed POMC transcription, the stop-gain variant (R218*) exhibited reduced inhibitory effect. The novel USP8 variant (P681Q) found in the contra-lateral tumor led to increased POMC transcription although weaker than the well characterized hotspot variant S718P, and did not affect EGFR ubiquitin. Interestingly, the patient also had a germline variant in the 21-alpha-hydroxylase gene (CYP21A2 p.A392T) though without clinical features of congenital adrenal hyperplasia.

conclusionWe report, for the first time, the genetic profiles of a patient with dual pituitary corticotroph tumors, identifying a stop-gain variant in GPR162 in one tumor and a novel USP8 variant (S718P) in the other. While both somatic variants increased POMC expression, only GPR162 R218* affected proliferation. We hypothesize that alterations in adrenal steroidogenesis due to the CYP21A1 mutation may have reduced negative feedback on corticotroph cells and acted in a permissive way to facilitate corticotroph tumorigenesis.

Indexed as

ACTH-Secreting Pituitary AdenomaAdenomaPituitary NeoplasmsAdultEndopeptidasesEndosomal Sorting Complexes Required for TransportFemaleHumansPro-OpiomelanocortinReceptors, G-Protein-CoupledUbiquitin ThiolesteraseEndopeptidasesEndosomal Sorting Complexes Required for TransportPro-OpiomelanocortinReceptors, G-Protein-CoupledUbiquitin ThiolesteraseUSP8 protein, humanCushing diseaseGPR162Single cell RNAseqUSP8Whole exosome sequencing

Identifiers

PMID40544420
PMCPMC12183135

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.