title: Genetic profile of 22 pancreatic carcinoma cell lines. Analysis of K-ras, p53, p16 and DPC4/Smad4.
abstract: The K-ras, p53, p16 and DPC4 genes are among those most frequently altered in pancreatic ductal carcinoma. We analyzed 22 cell lines for alterations in these genes by direct sequence analysis and methylation-specific polymerase chain reaction. These cell lines showed mutations in K-ras and p53 at frequencies of 91% and 95%, respectively. Alterations in p16INK4a were found in all cases and included nine homozygous deletions, seven mutations and promoter methylation in six cases. Eight cell lines (36%) had an alteration of DPC4, including one mutation and seven homozygous deletions. The most typical mutational profile involved K-ras, p53, and p16INK4a, concurrently aberrated in 20 cases (91%). Eight cell lines had alterations in all four genes. Inactivation of DPC4 was always accompanied by alteration of all of the other three genes. This comprehensive data regarding the cumulative genetic alterations in pancreatic carcinoma cell lines will be of great value for studies involving drug sensitivity or resistance that may be associated with inactivation of a particular gene or molecular pathway.
authors.affiliation: Department of Pathology, University of Verona, Italy.
authors.forename: P S
authors.initials: PS
authors.lastname: Moore
authors.forename: B
authors.initials: B
authors.lastname: Sipos
authors.forename: S
authors.initials: S
authors.lastname: Orlandini
authors.forename: C
authors.initials: C
authors.lastname: Sorio
authors.forename: F X
authors.initials: FX
authors.lastname: Real
authors.forename: N R
authors.initials: NR
authors.lastname: Lemoine
authors.forename: T
authors.initials: T
authors.lastname: Gress
authors.forename: C
authors.initials: C
authors.lastname: Bassi
authors.forename: G
authors.initials: G
authors.lastname: Klöppel
authors.forename: H
authors.initials: H
authors.lastname: Kalthoff
authors.forename: H
authors.initials: H
authors.lastname: Ungefroren
authors.forename: M
authors.initials: M
authors.lastname: Löhr
authors.forename: A
authors.initials: A
authors.lastname: Scarpa
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D019942:Genes, p16; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics*; D014407:Tumor Cells, Cultured
chemical_list: D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators