Article
Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.
Nature - 1 Feb 2018
Mueller Sebastian, Engleitner Thomas, Maresch Roman, Zukowska Magdalena, Lange Sebastian, Kaltenbacher Thorsten, Konukiewitz Björn, Öllinger Rupert, Zwiebel Maximilian, Strong Alex, Yen Hsi-Yu, Banerjee Ruby, Louzada Sandra, Fu Beiyuan, Seidler Barbara, Götzfried Juliana, Schuck Kathleen, Hassan Zonera, Arbeiter Andreas, Schönhuber Nina, Klein Sabine, Veltkamp Christian, Friedrich Mathias, Rad Lena, Barenboim Maxim, Ziegenhain Christoph, Hess Julia, Dovey Oliver M, Eser Stefan, Parekh Swati, Constantino-Casas Fernando, de la Rosa Jorge, Sierra Marta I, Fraga Mario, Mayerle Julia, Klöppel Günter, Cadiñanos Juan, Liu Pentao, Vassiliou George, Weichert Wilko, Steiger Katja, Enard Wolfgang, Schmid Roland M, Yang Fengtang, Unger Kristian, Schneider Günter, Varela Ignacio, Bradley Allan, Saur Dieter, Rad Roland
Abstract excerpt
The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus...
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