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There are currently few therapeutic options for patients with pancreatic cancer, and new insights into the pathogenesis of this lethal disease are urgently needed. Toward this end, we performed a comprehensive genetic analysis of 24 pancreatic cancers. We first determined the sequences of 23,219 transcripts, representing 20,661 protein-coding genes, in(More)
Aberrant DNA methylation and microRNA expression play important roles in the pathogenesis of pancreatic cancer. While interrogating differentially methylated CpG islands in pancreatic cancer, we identified two members of miR-200 family, miR-200a and miR-200b, that were hypomethylated and overexpressed in pancreatic cancer. We also identified prevalent(More)
Aberrant activation of the hedgehog (Hh) signaling pathway is one of the most prevalent abnormalities in human cancer. Tumors with cell autonomous Hh activation (e.g., medulloblastomas) can acquire secondary mutations at the Smoothened (Smo) antagonist binding pocket, which render them refractory to conventional Hh inhibitors. A class of Hh pathway(More)
Intraductal papillary mucinous neoplasms (IPMNs) are one of the three known curable precursor lesions of invasive pancreatic ductal adenocarcinoma, an almost uniformly fatal disease. Cell lines from IPMNs and their invasive counterparts should be valuable to identify gene mutations critical to IPMN carcinogenesis, and permit high-throughput screening to(More)
PURPOSE The goal of this study was to comprehensively identify CpG island methylation alterations between pancreatic cancers and normal pancreata and their associated gene expression alterations. EXPERIMENTAL DESIGN We employed methylated CpG island amplification followed by CpG island microarray, a method previously validated for its accuracy and(More)
PURPOSE Accumulating evidence suggests that cancer-associated stromal fibroblasts (CAF) contribute to tumor growth by actively communicating with cancer cells. Our aim is to identify signaling pathways involved in tumor-stromal cell interactions in human pancreatic cancer. EXPERIMENTAL DESIGN We established primary fibroblast cultures from human(More)
Cyclin-dependent kinase 5 (CDK5), a neuronal kinase that functions in migration, has been found to be activated in some human cancers in which it has been implicated in promoting metastasis. In this study, we investigated the role of CDK5 in pancreatic cancers in which metastatic disease is most common at diagnosis. CDK5 was widely active in pancreatic(More)
PURPOSE Cancer associated stromal fibroblasts (CAFs) undergo transcriptional and phenotypic changes that contribute to tumor progression, but the mechanisms responsible for these changes are not well understood. Aberrant DNA methylation is an important cause of transcriptional alterations in cancer cells but it is not known how important DNA methylation(More)
Purpose: MicroRNA (miRNA) alterations are likely to contribute to the development of pancreatic cancer and may serve as markers for the early detection of pancreatic neoplasia. Experimental Design: To identify the miRNA alterations that arise during the development of pancreatic cancer, we determined the levels of 735 miRNAs in 34 pancreatic intraepithelial(More)
PURPOSE The protein kinase B (AKT) pathway plays a key role in the regulation of cellular survival, apoptosis, and protein translation, and has been shown to have prognostic significance in a number of cancers. We sought to define its role in extrahepatic cholangiocarcinoma. EXPERIMENTAL DESIGN Two hundred twenty-one extrahepatic cholangiocarcinoma(More)