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Tumor-suppressive pathways in pancreatic carcinoma.

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 gene. 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.

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  • Authors+Show Affiliations

    ,

    Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2196, USA.

    , , , , , , , , ,

    Source

    Cancer research 57:9 1997 May 01 pg 1731-4

    MeSH

    Adenocarcinoma
    BRCA2 Protein
    Carrier Proteins
    Cyclin-Dependent Kinase Inhibitor p16
    DNA Mutational Analysis
    DNA, Neoplasm
    DNA-Binding Proteins
    Female
    Genes, Tumor Suppressor
    Genes, p53
    Genes, ras
    Heterozygote
    Humans
    Male
    Neoplasm Proteins
    Pancreatic Neoplasms
    Sequence Deletion
    Smad4 Protein
    Trans-Activators
    Transcription Factors

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    9135016

    Citation

    Rozenblum, E, et al. "Tumor-suppressive Pathways in Pancreatic Carcinoma." Cancer Research, vol. 57, no. 9, 1997, pp. 1731-4.
    Rozenblum E, Schutte M, Goggins M, et al. Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res. 1997;57(9):1731-4.
    Rozenblum, E., Schutte, M., Goggins, M., Hahn, S. A., Panzer, S., Zahurak, M., ... Kern, S. E. (1997). Tumor-suppressive pathways in pancreatic carcinoma. Cancer Research, 57(9), pp. 1731-4.
    Rozenblum E, et al. Tumor-suppressive Pathways in Pancreatic Carcinoma. Cancer Res. 1997 May 1;57(9):1731-4. PubMed PMID: 9135016.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Tumor-suppressive pathways in pancreatic carcinoma. AU - Rozenblum,E, AU - Schutte,M, AU - Goggins,M, AU - Hahn,S A, AU - Panzer,S, AU - Zahurak,M, AU - Goodman,S N, AU - Sohn,T A, AU - Hruban,R H, AU - Yeo,C J, AU - Kern,S E, PY - 1997/5/1/pubmed PY - 1997/5/1/medline PY - 1997/5/1/entrez SP - 1731 EP - 4 JF - Cancer research JO - Cancer Res. VL - 57 IS - 9 N2 - 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 gene. 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/9135016/Tumor_suppressive_pathways_in_pancreatic_carcinoma_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=9135016 DB - PRIME DP - Unbound Medicine ER -