Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 May;100(5):E783-8.
doi: 10.1210/jc.2014-4405. Epub 2015 Feb 19.

Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations

Bence Sipos  1 , Jan Sperveslage, Martin Anlauf, Maike Hoffmeister, Tobias Henopp, Stephan Buch, Jochen Hampe, Achim Weber, Pascal Hammel, Anne Couvelard, Walter Höbling, Wolfgang Lieb, Bernhard O Boehm, Günter Klöppel
Affiliations

Glucagon cell hyperplasia and neoplasia with and without glucagon receptor mutations

Bence Sipos et al. J Clin Endocrinol Metab. 2015 May.

Abstract

Context: Glucagon cell adenomatosis (GCA) was recently recognized as a multifocal hyperplastic and neoplastic disease of the glucagon cells unrelated to multiple endocrine neoplasia type 1 and von-Hippel-Lindau disease.

Objective: The study focused on the molecular analysis of the glucagon receptor (GCGR) gene in GCA and a description of the clinicopathological features of GCA with and without GCGR mutations.

Design: Pancreatic tissues from patients showing multiple glucagon cell tumors were morphologically characterized and macro- or microdissected. All exons of the GCGR gene were analyzed for mutations by Sanger and next-generation sequencing. Genotyping for all detected GCGR variants was performed in 2560 healthy individuals.

Patients: Six patients with GCA, and the parents of one patient were included in the study.

Main outcome measures: The main outcome measures were the correlations between the patients' GCGR mutation status and the respective clinicopathological data.

Results: GCGR germline mutations were found in three of six patients. Patient 1 harbored a homozygous stop mutation. This patient's parents showed an identical but heterozygous GCGR mutation. Patient 2 had two different heterozygous point mutations leading each to premature stop codons. Patient 3 exhibited two homozygous missense mutations. No GCGR mutations were identified in the three other patients and in a large cohort of healthy subjects. The patients harboring GCGR mutations exhibited a greater number of tumors and larger tumors than patients with wild-type GCGR. One of the patients with wild-type GCGR showed lymph node micrometastases.

Conclusions: GCA with GCGR germline mutations seems to follow an autosomal-recessive trait. By interrupting the GCGR signaling pathways GCGR mutations probably cause GCA via glucagon cell hyperplasia. GCA also occurs in patients without GCGR mutations, but seems to be associated with fewer and smaller tumors.

PubMed Disclaimer

LinkOut - more resources