Genetics of Carney Triad: Recurrent Losses at Chromosome 1 but Lack of Germline Mutations in Genes Associated with Paragangliomas and Gastrointestinal Stromal Tumors

• DOI: 10.1210/jc.2007-0797
• Publication Date: 2007-05-29T21:38:49Z
• Authors: Ludmila Matyakhina; Thalia A. Bei; Sarah R. McWhinney; Barbara Pasini; Silke Cameron; Bastian Gunawan; Sotirios G. Sterg...; Sosipatros Boikos; Michael Muchow; Amalia Dutra; Evgenia Pak; Elias Campo; Maria C. Cid; Fulgencio Gomez; Rolf C. Gaillard; Guillaume Assie; Laszlo Füzesi; Bora E. Baysal; Charis Eng; J. Aidan Carney; Constantine A. St...
• Keywords: SDHD; SDHB; PDGFRA; Comparative genomic hybridization; SDHA; Carney Complex

Context: Carney triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumors (GISTs) and pulmonary chondromas. Inactivating mutations mitochondrial complex II succinate dehydrogenase (SDH) enzyme subunits SDHB, SDHC, SDHD are found in PGLs, gain-of-function c-kit (KIT), platelet-derived growth factor receptor A (PDGFRA) GISTs. Objective: Our objective was to investigate possibility that patients CT and/or their may harbor SDHD, KIT, PDGFRA genes identify any other genetic alterations tumors. Design: Three males 34 females were studied retrospectively. We sequenced stated performed comparative genomic hybridization on a total 41 Results: No patient had coding sequence investigated genes. Comparative revealed number DNA copy changes: losses dominated among benign lesions, there an equal gains malignant average higher compared lesions. The most frequent greatest contiguous change 1q12-q21 deletion, region harbors SDHC gene. Another loss 1p. Allelic 1p 1q confirmed by fluorescent situ loss-of-heterozygosity studies. Conclusions: conclude is not due SDH-inactivating or KIT- PDGFRA-activating mutations. GISTs PGLs associated chromosome 1 changes appear participate tumor progression point common cause.