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

Milena Urbini, Annalisa Astolfi, Valentina Indio, Michael Heinrich, Christopher Corless, Margherita Nannini, Gloria Ravegnini, Guido Biasco, Maria A. Pantaleo

Research output: Contribution to journalArticle

13 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Article number87
JournalBMC Medical Genetics
Volume16
Issue number1
DOIs
StatePublished - Sep 28 2015

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Gastrointestinal Stromal Tumors
Methylation
Succinate Dehydrogenase
CpG Islands
Mutation
DNA Methylation
Epigenomics
Gene Expression
Messenger RNA

Keywords

  • dSDH GIST
  • GIST
  • Hypermethylation
  • Methylation
  • SDHC

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

SDHC methylation in gastrointestinal stromal tumors (GIST) : A case report. / Urbini, Milena; Astolfi, Annalisa; Indio, Valentina; Heinrich, Michael; Corless, Christopher; Nannini, Margherita; Ravegnini, Gloria; Biasco, Guido; Pantaleo, Maria A.

In: BMC Medical Genetics, Vol. 16, No. 1, 87, 28.09.2015.

Research output: Contribution to journalArticle

Urbini, M, Astolfi, A, Indio, V, Heinrich, M, Corless, C, Nannini, M, Ravegnini, G, Biasco, G & Pantaleo, MA 2015, 'SDHC methylation in gastrointestinal stromal tumors (GIST): A case report', BMC Medical Genetics, vol. 16, no. 1, 87. https://doi.org/10.1186/s12881-015-0233-7
Urbini, Milena ; Astolfi, Annalisa ; Indio, Valentina ; Heinrich, Michael ; Corless, Christopher ; Nannini, Margherita ; Ravegnini, Gloria ; Biasco, Guido ; Pantaleo, Maria A. / SDHC methylation in gastrointestinal stromal tumors (GIST) : A case report. In: BMC Medical Genetics. 2015 ; Vol. 16, No. 1.
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