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

BMC Medical Genetics

Maria A. Pantaleo³  Guido Biasco³  Gloria Ravegnini⁴  Margherita Nannini³  Christopher L. Corless¹  Michael C. Heinrich⁵  Valentina Indio²  Annalisa Astolfi²  Milena Urbini² 

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

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

Others  :  1230731
DOI  :  10.1186/s12881-015-0233-7

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

【 摘 要 】

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.

Case presentation

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.

Conclusion

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.

【 授权许可】

   
2015 Urbini et al.

【 图 表 】

Fig. 1.

Fig. 1.

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