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Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal adenocarcinomas: lack of mutations in the BRAF and EGFR genes

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Abstract

The vast majority of tumors of the pancreas are ductal adenocarcinomas. This cancer type has an extremely poor prognosis and in many Western countries, it represents the fifth leading cause of cancer-related death. Pancreatic ductal adenocarcinomas exhibit the highest incidence of activating KRAS (Ki-Ras) mutations observed in any human cancer. It was therefore of interest to examine how this pattern would relate to mutations in the BRAF and EGFR genes, which are involved in the same signaling pathway as KRAS. We screened a series of 43 formalin-fixed, paraffin-embedded ductal adenocarcinomas of the pancreas. When DNA was extracted from whole tissue sections, KRAS codon 12 mutations were detected in 67% of the tumors. When cancerous ducts were isolated by laser-assisted microdissection, 91% were positive for KRAS mutations. Although it did not reach statistical significance, there was a trend in our material that survival after diagnosis varied according to KRAS mutation subtype, GTT-positive patients having the best prognosis. No alterations in BRAF exons 11 and 15 or in EGFR exons 18–21 were detected in KRAS-positive or KRAS-negative cases. We therefore conclude that the BRAF and EGFR mutations commonly seen in a variety of human cancers are generally absent from pancreatic ductal adenocarcinomas. Apparently, these tumors depend on no more than one genetic hit in the EGFR-RAS-RAF signaling pathway.

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Acknowledgements

We thank Bendik Nordanger for expert technical assistance and Lars A. Akslen, Hanne Puntervoll, and Audny Hellebø for samples of positive control tissue. The study was supported by grants from the Meltzer Foundation, The Norwegian Cancer Society, and Helse Vest.

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Authors and Affiliations

  1. Section for Pathology, The Gade Institute, University of Bergen, Haukeland University Hospital, Bergen N-5021, Norway

    Heike Immervoll, Kalaiarasy Kugarajh, Solrun J. Steine & Anders Molven

  2. Department of Pathology, Haukeland University Hospital, Bergen, Norway

    Heike Immervoll & Anders Molven

  3. Department of Surgery, Haukeland University Hospital, Bergen, Norway

    Dag Hoem

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  1. Heike Immervoll
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  2. Dag Hoem
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Correspondence to Anders Molven.

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Immervoll, H., Hoem, D., Kugarajh, K. et al. Molecular analysis of the EGFR-RAS-RAF pathway in pancreatic ductal adenocarcinomas: lack of mutations in the BRAF and EGFR genes. Virchows Arch 448, 788–796 (2006). https://doi.org/10.1007/s00428-006-0191-8

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  • DOI: https://doi.org/10.1007/s00428-006-0191-8

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