Titre
Genetics of carney triad: recurrent losses at chromosome 1 but lack of germline mutations in genes associated with paragangliomas and gastrointestinal stromal tumors
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Auteur(s)
Matyakhina, L.
Auteure/Auteur
Bei, T. A.
Auteure/Auteur
McWhinney, S. R.
Auteure/Auteur
Pasini, B.
Auteure/Auteur
Cameron, S.
Auteure/Auteur
Gunawan, B.
Auteure/Auteur
Stergiopoulos, S. G.
Auteure/Auteur
Boikos, S.
Auteure/Auteur
Muchow, M.
Auteure/Auteur
Dutra, A.
Auteure/Auteur
Pak, E.
Auteure/Auteur
Campo, E.
Auteure/Auteur
Cid, M. C.
Auteure/Auteur
Gomez, F.
Auteure/Auteur
Gaillard, R. C.
Auteure/Auteur
Assie, G.
Auteure/Auteur
Fuzesi, L.
Auteure/Auteur
Baysal, B. E.
Auteure/Auteur
Eng, C.
Auteure/Auteur
Carney, J. A.
Auteure/Auteur
Stratakis, C. A.
Auteure/Auteur
Liens vers les personnes
rgaillar
Liens vers les unités
ISSN
0021-972X
Statut éditorial
Publié
Date de publication
2007-08
Volume
92
Numéro
8
Première page
2938
Dernière page/numéro d’article
43
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't --- Old month value: Aug
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't --- Old month value: Aug
Résumé
CONTEXT: Carney triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumors (GISTs) and pulmonary chondromas. Inactivating mutations of the mitochondrial complex II succinate dehydrogenase (SDH) enzyme subunits SDHB, SDHC, and SDHD are found in PGLs, gain-of-function mutations of c-kit (KIT), and platelet-derived growth factor receptor A (PDGFRA) in GISTs. OBJECTIVE: Our objective was to investigate the possibility that patients with CT and/or their tumors may harbor mutations of the SDHB, SDHC, SDHD, KIT, and PDGFRA genes and identify any other genetic alterations in CT tumors. DESIGN: Three males and 34 females with CT were studied retrospectively. We sequenced the stated genes and performed comparative genomic hybridization on a total of 41 tumors. RESULTS: No patient had coding sequence mutations of the investigated genes. Comparative genomic hybridization revealed a number of DNA copy number changes: losses dominated among benign lesions, there were an equal number of gains and losses in malignant lesions, and the average number of alterations in malignant tumors was higher compared with benign lesions. The most frequent and greatest contiguous change was 1q12-q21 deletion, a region that harbors the SDHC gene. Another frequent change was loss of 1p. Allelic losses of 1p and 1q were confirmed by fluorescent in situ hybridization and loss-of-heterozygosity studies. CONCLUSIONS: We conclude that CT is not due to SDH-inactivating or KIT- and PDGFRA-activating mutations. GISTs and PGLs in CT are associated with chromosome 1 and other changes that appear to participate in tumor progression and point to their common genetic cause.
Sujets
PID Serval
serval:BIB_A2AA32CDA09E
PMID
Open Access
Oui
Date de création
2008-02-15T15:57:44.669Z
Date de création dans IRIS
2025-05-21T04:49:28Z