Genetic profile of 22 pancreatic carcinoma cell lines: Analysis of K-ras, p53, p16 and DPC4/Smad4

Patrick S. Moore, Bence Sipos, Simonetta Orlandini, Claudio Sorio, Francisco X. Real, Nicholas R. Lemoine, Thomas Gress, Claudio Bassi, Günter Klöppel, Holger Kalthoff, Hendrik Ungefroren, Matthias Löhr, Aldo Scarpa

Research output: Contribution to journalArticlepeer-review

301 Scopus citations

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.

Original languageEnglish
Pages (from-to)798-802
Number of pages5
JournalVirchows Archiv
Volume439
Issue number6
DOIs
StatePublished - 2001
Externally publishedYes

Keywords

  • Carcinoma cell lines
  • DPC4/Smad4
  • K-ras
  • P16
  • P53
  • Pancreas

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