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Inflammatory fibroid polyps harbour mutations in the platelet‐derived growth factor receptor alpha ( PDGFRA) gene
Author(s) -
Schildhaus HU,
Cavlar T,
Binot E,
Büttner R,
Wardelmann E,
MerkelbachBruse S
Publication year - 2008
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2393
Subject(s) - pdgfra , cancer research , biology , inflammatory fibroid polyp , mutation , exon , pathology , gastrointestinal tract , stromal cell , medicine , gene , genetics , gist , biochemistry
Inflammatory fibroid polyps (IFPs) are mesenchymal tumours which arise in the submucosa and mucosa of the gastrointestinal tract. To date, the pathogenesis is unknown and IFPs are considered reactive and non‐neoplastic lesions. Investigating a series of 23 IFPs, we made the observation that the tumours consistently express PDGFRA. To further elucidate the pathogenetic role of PDGFRA , we performed mutational analyses of exons 10, 12, 14, and 18. As IFPs are characterized by an inflammatory infiltrate rich in eosinophils, we used fluorescence in situ hybridization in a subset of tumours to investigate a possible FIP1L1–PDGFRA translocation which is known as the cause of hypereosinophilic syndrome (HES). Sixteen IFPs (70%) harboured activating mutations in exons 12 and 18, respectively: V561D ( n = 1), R560SΔ561–567 ( n = 1), Δ559–561D591H ( n = 1), S566RΔ567–571 ( n = 3), D842V ( n = 7), D842I ( n = 1), Δ842–845 ( n = 1), and Δ845–848 ( n = 1). These mutations equal pathogenic mutations detected in gastrointestinal stromal tumours previously. Activating mutations in exons 10 and 14 were not noted. None of the cases revealed the FIP1L1–PDGFRA translocation. Considering the remarkable number of activating mutations detected in our series, we conclude that the vast majority of IFPs harbour gain‐of‐function mutations in the PDGFRA gene. The presence of PDGFRA mutations questions the reactive nature of IFPs and raises the possibility of a neoplastic process. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.