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Metabolism

Epigenetic links to the web of Krebs

Nature Reviews Cancer volume 13, page 437 (2013)Cite this article

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To examine the effects of SDH mutations on gastrointestinal stromal tumour (GIST) epigenomes, Killian et al. characterized the 5-methyl cytosine (5mC) DNA methylation profiles of 24 SDH-mutant GIST samples compared with 39 GISTs that harboured mutations in the KIT kinase pathway and also with various normal tissues. Whereas DNA methylation in KIT-mutant GISTs was generally similar to that of normal tissues, SDH-mutant GISTs showed characteristic hypermethylation patterns. Furthermore, similar DNA hypermethylation occurred in 20 SDH-mutant versus nine SDH-wild-type paragangliomas and pheochromocytomas.

Interestingly, KIT-mutant GISTs had relatively unstable genomes, with frequent copy number alterations, compared with SDH-mutant GISTs, which had remarkably stable genomes. Such findings suggest that an altered epigenome in SDH-mutant GISTs might be sufficient to be an oncogenic driver in the absence of widespread genetic alterations.

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References

  1. Killian, J. K. et al. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor. Cancer Discov. 3, 648–657 (2013)

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  2. Letouzé, E. et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 21 May 2013 (10.1016/j.ccr.2013.04.018)

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  1. Darren J. Burgess
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Burgess, D. Epigenetic links to the web of Krebs. Nat Rev Cancer 13, 437 (2013). https://doi.org/10.1038/nrc3551

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