title: SDHC methylation in gastrointestinal stromal tumors (GIST): a case report.
abstract: BACKGROUND
  Gastrointestinal stromal tumors (GIST) recently have been recognized as a genetically and biologically heterogeneous disease. In addition to KIT or PDGFRA mutated GIST, mutational inactivation of succinate dehydrogenase (SDH) subunits has been detected in the KIT/PDGFRA wild-type subgroup, referred to as SDH deficient (dSDH). Even though most dSDH GIST harbor mutations in SDHx subunit genes, some are SDHx wild type. Epigenetic regulation by DNA methylation of CpG islands recently has been found to be an alternative mechanism underlying the lack of SDH complex in GIST.
  
  
  METHODS
  We report a particular case of dSDH GIST, previously analyzed with microarrays and next-generation sequencing, for which no molecular pathogenetic events have been identified. Gene expression analysis showed remarkable down-modulation of SDHC mRNA with respect to all other GIST samples, both SDHA-mutant and KIT/PDGFRA-mutant GIST. By a bisulfite methylation assay targeted to 2 SDHC CpG islands, we detected hypermethylation of the SDHC promoter.
  
  
  CONCLUSIONS
  Herein we report an additional case of dSDH GIST without SDHx mutation but harboring hypermethylation in the SDHC promoter, thus confirming the complexity of the molecular background of this subtype of GIST.
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, via Massarenti 11, 40138, Bologna, Italy. milena.urbini@yahoo.com.
authors.forename: Milena
authors.initials: M
authors.lastname: Urbini
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, via Massarenti 11, 40138, Bologna, Italy. annalisa.astolfi@unibo.it.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Astolfi
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, via Massarenti 11, 40138, Bologna, Italy. valentina.indio2@unibo.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Indio
authors.affiliation: VA Portland Health Care System and OHSU Knight Cancer Institute, and Division of Hematology and Oncology, Oregon Health & Science University, Portland, Oregon, USA. heinrich@ohsu.edu.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Heinrich
authors.affiliation: Department of Pathology and OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA. corlessc@ohsu.edu.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.affiliation: Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. margherita.nannini@unibo.it.
authors.forename: Margherita
authors.initials: M
authors.lastname: Nannini
authors.affiliation: Department of Pharmacy and Biotechnology, FaBit, University of Bologna, Bologna, Italy. gloria.ravegnini2@unibo.it.
authors.forename: Gloria
authors.initials: G
authors.lastname: Ravegnini
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, via Massarenti 11, 40138, Bologna, Italy. guido.biasco@unibo.it.|Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. guido.biasco@unibo.it.
authors.forename: Guido
authors.initials: G
authors.lastname: Biasco
authors.affiliation: "Giorgio Prodi" Cancer Research Center, University of Bologna, via Massarenti 11, 40138, Bologna, Italy. maria.pantaleo@unibo.it.|Department of Specialized, Experimental and Diagnostic Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. maria.pantaleo@unibo.it.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pantaleo
mesh_terms: D000328:Adult; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000201:enzymology / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011401:Promoter Regions, Genetic
chemical_list: D008565:Membrane Proteins; C108096:SDHC protein, human