title: Genetics of carney triad: recurrent losses at chromosome 1 but lack of germline mutations in genes associated with paragangliomas and gastrointestinal stromal tumors.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Section on Endocrinology and Genetics, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Matyakhina
authors.forename: Thalia A
authors.initials: TA
authors.lastname: Bei
authors.forename: Sarah R
authors.initials: SR
authors.lastname: McWhinney
authors.forename: Barbara
authors.initials: B
authors.lastname: Pasini
authors.forename: Silke
authors.initials: S
authors.lastname: Cameron
authors.forename: Bastian
authors.initials: B
authors.lastname: Gunawan
authors.forename: Sotirios G
authors.initials: SG
authors.lastname: Stergiopoulos
authors.forename: Sosipatros
authors.initials: S
authors.lastname: Boikos
authors.forename: Michael
authors.initials: M
authors.lastname: Muchow
authors.forename: Amalia
authors.initials: A
authors.lastname: Dutra
authors.forename: Evgenia
authors.initials: E
authors.lastname: Pak
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Maria C
authors.initials: MC
authors.lastname: Cid
authors.forename: Fulgencio
authors.initials: F
authors.lastname: Gomez
authors.forename: Rolf C
authors.initials: RC
authors.lastname: Gaillard
authors.forename: Guillaume
authors.initials: G
authors.lastname: Assie
authors.forename: Laszlo
authors.initials: L
authors.lastname: Füzesi
authors.forename: Bora E
authors.initials: BE
authors.lastname: Baysal
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: J Aidan
authors.initials: JA
authors.lastname: Carney
authors.forename: Constantine A
authors.initials: CA
authors.lastname: Stratakis
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics*; D018628:Gene Dosage; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D009693:Nucleic Acid Hybridization; D010235:Paraganglioma / Q000235:genetics*; D012189:Retrospective Studies; D013385:Succinate Dehydrogenase / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D013385:Succinate Dehydrogenase