title: Epithelioid gastric stromal tumours of the antrum in young females with the Carney triad: a report of three new cases with mutational analysis and comparative genomic hybridization.
abstract: Carney triad is a rare non-hereditary condition affecting young females and characterized by metachronous or synchronous occurrence of epithelioid gastrointestinal stromal tumours (GISTs), pulmonary chondroma and extra-adrenal paraganglioma. The genetic alterations in Carney triad-related GISTs have not been well studied. We evaluated GISTs from three females with incomplete Carney triad for KIT and PDGFRA mutations and studied the DNA by comparative genomic hybridization (CGH). All GISTs originated in the antrum and had a monotonous epithelioid morphology. Two patients had GISTs and pulmonary chondroma and one had GISTs and paraganglioma. Initial manifestation was GIST (n=1), pulmonary chondroma (n=1) and bladder paraganglioma (n=1). Time to the second component was 2-13 years. Two patients were alive at 108 and 168 months (one with metastases) and one died of the disease 3 years later. All cases were wild-type for KIT exons 9, 11, 13, 17 and PDGFRA exons 12 and 18. CGH revealed 14 aberrations (mean, 4.7/tumour) including 11 gains (X, 1q, 5p, 8q, 9p, 12p, 13q, 18p, 19q), 2 amplifications (1q, 19p) and one loss (13q). Carney triad-related GISTs do not only lack conventional KIT and PDGFRA mutations, but they also lack the non-random loss of 14q and 22q characteristic of their sporadic counterparts, suggesting an origin through a distinct pathogenetic pathway.
authors.affiliation: Institute of Pathology, Klinikum Nürnberg, 90419 Nürnberg, Germany. abbas.agaimy@klinikum-nuernberg.de
authors.forename: Abbas
authors.initials: A
authors.lastname: Agaimy
authors.forename: Antje-Friederike
authors.initials: AF
authors.lastname: Pelz
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Peter H
authors.initials: PH
authors.lastname: Wünsch
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dietmaier
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
authors.forename: Peter
authors.initials: P
authors.lastname: Wieacker
authors.forename: Albert
authors.initials: A
authors.lastname: Roessner
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Regine
authors.initials: R
authors.lastname: Schneider-Stock
mesh_terms: D000328:Adult; D002812:Chondroma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D009693:Nucleic Acid Hybridization; D010236:Paraganglioma, Extra-Adrenal / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011706:Pyloric Antrum / Q000473:pathology*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013577:Syndrome
chemical_list: D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha