Tumor-suppressive pathways in pancreatic carcinoma

Ester Rozenblum, Mieke Schutte, Michael Goggins, Stephan A. Hahn, Shawn Panzer, Marianna Zahurak, Steven N. Goodman, Taylor A. Sohn, Ralph H. Hruban, Charles J. Yeo, Scott E. Kern

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    Abstract

    During tumorigenesis, positive selection is exerted upon those tumor cells that alter rate-limiting regulatory pathways. A corollary of this principle is that mutation of one gene abrogates the need for alteration of another gene in the same pathway and also that the coexistence in a single tumor of mutations in different genes implies their involvement in distinct tumor-suppressive pathways. We studied 42 pancreatic adenocarcinomas for genetic alterations in the K-ras oncogene and the p16, p53, and DPC4 tumor suppressor genes. All of them had the K-ras gene mutated. Thirty-eight % of the tumors had four altered genes, another 38% had three altered genes, 15% had two altered genes, and 8% of the tumors had one altered gone. Interestingly, we noted a high concordance of DPC4 and p16 inactivations (P = 0.007), suggesting that the genetic inactivation of p16 increases the selective advantage of subsequent mutation in DPC4. No statistically significant association was identified between the alteration of these cancer genes and pathological or clinical parameters. This type of multigenic analysis in human tumors may serve to substantiate experimental tumor models and thus increase our understanding of the truly physiologically relevant tumor-suppressive pathways that are abrogated during human tumorigenesis.

    Original languageEnglish (US)
    Pages (from-to)1731-1734
    Number of pages4
    JournalCancer Research
    Volume57
    Issue number9
    StatePublished - May 1 1997

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    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Cite this

    Rozenblum, E., Schutte, M., Goggins, M., Hahn, S. A., Panzer, S., Zahurak, M., Goodman, S. N., Sohn, T. A., Hruban, R. H., Yeo, C. J., & Kern, S. E. (1997). Tumor-suppressive pathways in pancreatic carcinoma. Cancer Research, 57(9), 1731-1734.