Pancreatic carcinogenesis.

Pancreatic cancer is an almost universally lethal disease. Research over the last two decades has shown that pancreatic cancer is fundamentally a genetic disease, caused by inherited germline and acquired somatic mutations in cancer-associated genes. Multiple alterations in genes that are important in pancreatic cancer progression have been identified, including tumor suppressor genes, oncogenes, and genome maintenance genes.

Differentiating pancreatic lesions by microarray and QPCR analysis of pancreatic juice RNAs.

Background: The gene expression profile of pancreatic cancer is significantly different from that of normal pancreas. Differences in gene expression are detectable using microarrays, but microarrays have traditionally been applied to pancreatic cancer tissue obtained from surgical resection. We hypothesized that gene expression alterations indicative of pancreatic cancer can be detected by profiling the RNA of pancreatic juice.

Increased cyclooxygenase-2 expression in duodenal compared with colonic tissues in familial adenomatous polyposis and relationship to the -765G -> C COX-2 polymorphism.

Background: Colorectal cancers arising in patients with familial adenomatous polyposis (FAP) can be largely prevented by polyp surveillance and prophylactic colectomy. As a result, duodenal adenocarcinoma has become a leading cause of death in patients with FAP. Cyclooxygenase 2 (COX-2) inhibition is effective against colorectal polyposis in FAP, but is less effective in treating duodenal polyps.

Expression and prognostic significance of 14-3-3sigma and ERM family protein expression in periampullary neoplasms.

Aberrant gene expression in pancreatic ductal adenocarcinomas contributes to the dismal outcome of patients who develop this disease. The 5' region of 14-3-3sigma (stratifin) is hypomethylated in pancreatic adenocarcinomas and is associated with gene overexpression. In multiple experimental systems, ezrin (ERM, Radixin, Moesin) has been identified as being important in the metastatic behavior of pancreatic and other cancers.

Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion.

The p16INK4A/CDKN2A (p16) gene on chromosome 9p21 is inactivated in >90% of invasive pancreatic cancers. In 40% of pancreatic cancers the p16 gene is inactivated by homozygous deletion, in 40% by an intragenic mutation coupled with loss of the second allele, and in 10-15% by hypermethylation of the p16 gene promoter. Immunohistochemical labeling for the p16 gene product parallels gene status, but does not provide information of the mechanism of p16 gene inactivation.

Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: a potential new target for therapy.

Methylthioadenosine phosphorylase (MTAP) plays an important role in the salvage pathway for the synthesis of adenosine. Novel chemotherapeutic strategies exploiting the selective loss of MTAP function in cancers have been proposed. The MTAP gene, on chromosome 9p21, is frequently included within homozygous deletions of the p16INK4A/ CDKN2A gene.

Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression.

Serial analysis of gene expression (SAGE) is a powerful tool for the discovery of novel tumor markers. The publicly available online SAGE libraries of normal and neoplastic tissues (http://www.ncbi.

Identification of novel highly expressed genes in pancreatic ductal adenocarcinomas through a bioinformatics analysis of expressed sequence tags.

In most microarray experiments, a significant fraction of the differentially expressed mRNAs identified correspond to expressed sequence tags (ESTs) and are generally discarded from further analyses. We used careful bioinformatics analyses to characterize those ESTs that were found to be highly overexpressed in a series of pancreatic adenocarcinomas. cDNA was prepared from 60 non-neoplastic samples (normal pancreas [n = 20], normal colon [n = 10], or normal duodenal mucosal [n = 30]) and from 64 pancreatic cancers (resected cancers [n = 50] or cancer cell lines [n = 14]) and hybridized to the complete Affymetrix Human Genome U133 GeneChip(R) set (arrays U133A and B) for simultaneous analysis of 45,000 fragments corresponding to 33,000 known genes and 6,000 ESTs.