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
Case Reports
. 2007 Sep;92(9):3728-32.
doi: 10.1210/jc.2007-0894. Epub 2007 Jun 12.

Multiple gastrointestinal stromal and other tumors caused by platelet-derived growth factor receptor alpha gene mutations: a case associated with a germline V561D defect

Affiliations
Case Reports

Multiple gastrointestinal stromal and other tumors caused by platelet-derived growth factor receptor alpha gene mutations: a case associated with a germline V561D defect

Barbara Pasini et al. J Clin Endocrinol Metab. 2007 Sep.

Abstract

Context: Gastrointestinal stromal tumors (GISTs) may be caused by somatic or germline mutations of the KIT and PDGFRA genes, but most GISTs associated with neuroendocrine tumors (NETs) are not, suggesting that other molecular pathways are implicated in their pathogenesis.

Objective: In the course of investigating NETs and GIST genetics, we encountered a patient who had a unique combination of multiple fibrous polyps and lipomas of the small intestine and several gastric GISTs.

Design: The study included the clinical description of a unique patient, DNA sequencing of germline and tumor DNA, and comparative genomic hybridization (CGH) and allelic marker analysis of tumor DNA.

Results: The patient was found to carry a germline PDGFRA mutation (V561D) in the heterozygote state; it has only been seen rarely before and only in the somatic state in sporadic GISTs. CGH identified losses of chromosomal regions 1p33-36, 9q12-24, 11q13, and 16q; loss of the 14q region that is commonly lost in NETs and GISTs was shown by DNA marker analysis. These changes are likely to point to secondary and tertiary genetic hits involved in the formation of these rare tumors.

Conclusions: Multiple GISTs and other tumors may be caused by germline PDGFRA gene mutations; the V561D mutation can occur in the germline state and lead to a syndrome that should not be confused with other genetic conditions associated with a predisposition to NETs and other tumors. A number of chromosomal loci are likely to be involved in the PDGFRA V561D-dependent tumorigenesis, as shown by CGH and other DNA analyses.

PubMed Disclaimer

Publication types

LinkOut - more resources