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Accession IconGSE17891

Pervasive subtypes of pancreatic ductal adenocarcinoma (PDA) and their differing response to therapy.

Organism Icon Homo sapiens, Mus musculus
Sample Icon 61 Downloadable Samples
Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)

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Description
Pancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA.
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