Cited by 329Pancreatic and Hepatic Oncology ResearchCancer Genomics and DiagnosticsGenetic factors in colorectal cancer

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

Moore, Patrick S., Sipos, Bence, Orlandini, Simonetta, Sorio, Claudio, Real, Francisco X., Lemoine, Nicholas R., Gress, Thomas, Bassi, Claudio +5 more·2001·Virchows Archiv

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.

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Crossref · 10.1007/s004280100474

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  • Homozygous deletion of DPC4 occurs in 32% of PDAC cell lines and is exclusively present in cases with concurrent alterations in K-ras, p53 and p16.

    “Homozygous deletion of DPC4 was found in 32% of cases, exclusively present in cases with concurrent alterations in K-ras, p53 and p16.”
  • DPC4 inactivation is a late-stage event in pancreatic carcinoma pathogenesis.

    “This suggests that DPC4 inactivation is a late-stage event in pancreatic carcinoma pathogenesis [67].”

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Authors
Moore, P. S., Sipos, B., Orlandini, S., Sorio, C., Real, F. X., Lemoine, N. R., Gress, T., Bassi, C., Klöppel, G., Kalthoff, H., Ungefroren, H., Löhr, M., & Scarpa, A.
Affiliations
  • University of Verona (IT)
  • Christian-Albrechts-Universität zu Kiel (DE)
  • Municipal Institute for Medical Research (ES)
  • Imperial College London (GB)
  • Universität Ulm (DE)
  • Heidelberg University (DE)
Corresponding author
Scarpa, Aldo
Venue
Virchows Archiv
Published
2001-12
Volume
439
Issue
6
Pages
798-802
ISSN
  • 0945-6317 (ISSN-L)
  • 1432-2307
OpenAlex
W2037386039
Cited by
329
References
37
Citations by year
2026: 6 · 2025: 4 · 2024: 9 · 2023: 8 · 2022: 13 · 2021: 16 · 2020: 5 · 2019: 12 · 2018: 14 · 2017: 12 · 2016: 23 · 2015: 15 · 2014: 18 · 2013: 13 · 2012: 12
FWCI
5.61
Type
journal article
Language
en
Open access
closed
Locations
  • Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords
pancreatic ductal carcinoma, KRAS mutation, TP53 mutation, p16INK4a, SMAD4, homozygous deletion, promoter methylation, genetic alterations, mutational landscape, drug sensitivity and resistance
MeSH terms
DNA Mutational Analysis, DNA-Binding Proteins, DNA, Neoplasm, Humans, Mutation, Pancreatic Neoplasms, Genes, ras, Tumor Cells, Cultured, Trans-Activators, Polymerase Chain Reaction, Genes, p53, Genes, p16, Carcinoma, Pancreatic Ductal, Smad4 Protein

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