Genetics of carney triad: recurrent losses at chromosome 1 but lack of germline mutations in genes associated with paragangliomas and gastrointestinal stromal tumors


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Genetics of carney triad: recurrent losses at chromosome 1 but lack of germline mutations in genes associated with paragangliomas and gastrointestinal stromal tumors
Journal of Clinical Endocrinology and Metabolism
Matyakhina  L., Bei  T. A., McWhinney  S. R., Pasini  B., Cameron  S., Gunawan  B., Stergiopoulos  S. G., Boikos  S., Muchow  M., Dutra  A., Pak  E., Campo  E., Cid  M. C., Gomez  F., Gaillard  R. C., Assie  G., Fuzesi  L., Baysal  B. E., Eng  C., Carney  J. A., Stratakis  C. A.
0021-972X (Print)
Statut éditorial
Date de publication
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
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.
Adolescent Adult Child Chromosomes, Human, Pair 1/*genetics DNA, Neoplasm/genetics Female Gastrointestinal Neoplasms/*genetics Gastrointestinal Stromal Tumors/*genetics Gene Dosage Germ-Line Mutation/*genetics Humans Immunohistochemistry In Situ Hybridization, Fluorescence Loss of Heterozygosity Lung Neoplasms/*genetics Male Nucleic Acid Hybridization Paraganglioma/*genetics Retrospective Studies Succinate Dehydrogenase/genetics Tumor Cells, Cultured
Web of science
Open Access
Création de la notice
15/02/2008 16:57
Dernière modification de la notice
20/08/2019 15:08
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