SDHC methylation in gastrointestinal stromal tumors (GIST): a case report

BMC Medical Genetics

Case Report

Christopher L. Corless¹  Gloria Ravegnini²  Margherita Nannini³  Michael C. Heinrich⁴  Milena Urbini⁵  Annalisa Astolfi⁵  Valentina Indio⁵  Guido Biasco⁶  Maria A. Pantaleo⁶ 

[1] Department of Pathology and OHSU Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, USA;Department of Pharmacy and Biotechnology, FaBit, University of Bologna, Bologna, Italy;Department of Specialized, Experimental and Diagnostic Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy;VA Portland Health Care System and OHSU Knight Cancer Institute, and Division of Hematology and Oncology, Oregon Health & Science University, Portland, Oregon, USA;“Giorgio Prodi” Cancer Research Center, University of Bologna, via Massarenti 11, 40138, Bologna, Italy;“Giorgio Prodi” Cancer Research Center, University of Bologna, via Massarenti 11, 40138, Bologna, Italy;Department of Specialized, Experimental and Diagnostic Medicine, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy;

关键词: SDHC;    Methylation;    Hypermethylation;    GIST;    dSDH GIST;   

DOI  :  10.1186/s12881-015-0233-7

 received in 2015-05-12, accepted in 2015-09-21,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundGastrointestinal 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.Case presentationWe 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.ConclusionHerein 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.

【 授权许可】

CC BY   
© Urbini et al. 2015