title: Analysis of genomic DNA alterations and mRNA expression patterns in a panel of human pancreatic cancer cell lines.
abstract: Genomic alterations influencing the expression and/or activity of tumor suppressors or oncogenes such as KRAS2, CDKN2A, TP53, and DPC4 have been directly implicated in the initiation and progression of human pancreatic adenocarcinoma. In an effort further to systematically characterize the genomic alterations that occur in this disease, we conducted a genome wide analysis of alterations in gene copy number using array-based comparative genomic hybridization (CGH). For this analysis, we utilized a panel of 25 human pancreatic cancer cell lines derived from either primary or metastatic tumors. This panel also included a metastatic progression series of cell lines derived from COLO 357 cells. Array CGH permitted the identification of alterations in the copy number of genes that might participate in the aberrant behavior of pancreatic cancer cells. In addition, the acquisition of invasive and metastatic potential by derivatives of COLO 357 cells was accompanied by additional focal genomic alterations including point mutations and amplification of KRAS2. To complement the array CGH analysis, we also conducted an analysis of mRNA expression patterns in a subset of these cells using cDNA microarrays. By this means, we identified a set of candidate genes, including those regulated by RAS signaling, that may contribute to the process of cancer cell invasion and metastasis. Supplementary material for this article can be found on the Genes, Chromosomes, and Cancer website at http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html.
authors.affiliation: Cancer Research Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco Comprehensive Cancer Center, San Francisco, California, USA.
authors.forename: Stephan
authors.initials: S
authors.lastname: Gysin
authors.forename: Paula
authors.initials: P
authors.lastname: Rickert
authors.forename: Kumar
authors.initials: K
authors.lastname: Kastury
authors.forename: Martin
authors.initials: M
authors.lastname: McMahon
mesh_terms: D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000235:genetics*; D005784:Gene Amplification; D006801:Humans; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics*; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D018631:ras Proteins
chemical_list: D004273:DNA, Neoplasm; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins