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dc.contributor.authorMiller, Michael R
dc.contributor.authorMa, Deqin
dc.contributor.authorSchappet, James
dc.contributor.authorBreheny, Patrick
dc.contributor.authorMott, Sarah L
dc.contributor.authorBannick, Nadine
dc.contributor.authorAskeland, Eric
dc.contributor.authorBrown, James
dc.contributor.authorHenry, Michael D
dc.date.accessioned2015-09-01T17:03:51Z
dc.date.available2015-09-01T17:03:51Z
dc.date.issued2015-07-30
dc.identifier.citationMolecular Cancer. 2015 Jul 30;14(1):141
dc.identifier.urihttp://dx.doi.org/10.1186/s12943-015-0416-z
dc.identifier.urihttp://hdl.handle.net/10724/31718
dc.description.abstractAbstract Background Dystroglycan (DG) is a cell-surface laminin receptor that links the cytoskeleton to the extracellular matrix in a variety of epithelial tissues. Its function as a matrix receptor requires extensive glycosylation of its extracellular subunit αDG, which involves at least 13 distinct genes. Prior work has shown loss of αDG glycosylation in an assortment of carcinomas, including clear cell renal cell carcinoma (ccRCC) though the cause (s) and functional consequences of this loss are still unclear. Methods Using The Cancer Genome Atlas (TCGA) database, we analyzed the DG glycosylation pathway to identify changes in mRNA expression and correlation with clinical outcomes. We validated our findings with a cohort of 65 patients treated with radical nephrectomy by analyzing DG glycosylation via immunohistochemistry and gene expression via qRT-PCR. Results Analysis of TCGA database revealed frequent dysregulation of a subset of DG glycosyltransferases. Most notably, there was a frequent, significant downregulation of GYLTL1B (LARGE2) and ISPD. DG glycosylation is frequently impaired in ccRCC patient samples and most strongly associates with downregulation of GYLTL1B. Conclusions Reduced levels of GYLTL1B and ISPD mRNA associated with increased patient mortality and are the likely cause of αDG hypoglycosylation in ccRCC.
dc.titleDownregulation of dystroglycan glycosyltransferases LARGE2 and ISPD associate with increased mortality in clear cell renal cell carcinoma
dc.typeJournal Article
dc.date.updated2015-07-29T18:17:08Z
dc.language.rfc3066en
dc.rights.holderMiller et al.


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