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K-ras mutations and allelic loss at 5q and 18q in the development of human pancreatic cancers

  • Original Articles
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Summary

Conclusion

Our findings have implications for early diagnosis and for the identification of patients at increased risk.

Background

Invasive cancers of the pancreas frequently are preceded by and associated with a spectrum of preneoplastic changes. We investigated the presence of K-ras mutations and allelic loss at 5q and 18q loci in preneoplastic lesions associated with nine cases of invasive pancreatic ductal carcinomas.

Methods

We precisely microdissected 115 foci of normal, preinvasive, and invasive foci from paraffinembedded sections.

Results

  1. 1.

    K-ras mutations occur early in the pathogenesis of pancreatic adenocarcinoma. Mutations were identified in multiple preneoplastic foci associated with all six cases in whichras mutations were present in the corresponding invasive cancers, including nearly all foci of mucous cell and atypical hyperplasia, in some cases of papillary hyperplasia (40%), and in one example of morphologically normal epithelium.

  2. 2.

    Ras mutations in preneoplastic foci are widespread, occur distant from the invasive tumor, and may present multiple mutations. Two, and in one case three, different types of K-ras mutations were found in separate preneoplastic foci from three individual cases.

  3. 3.

    Evidence for a “second hit” in theras gene (i.e., loss of wild-type allele or amplification of the mutant allele) was present in some tumors and may be associated with the invasive process.

  4. 4.

    In contrast toras mutations, limited data suggest that loss of heterozygosity (LOH) at 5q and 18q are relatively late events.

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Author notes

  1. Kenji Sugio

    Present address: Department of Surgery II, Faculty of Medicine, Kyushu University, 812-82, Fukuoka, Japan

Authors and Affiliations

  1. Division of Anatomic Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX

    Kyle Molberg & Jorge Albores-Saavedra

  2. Department of Pathology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX

    Kyle Molberg, Jorge Albores-Saavedra & Adi F. Gazdar

  3. Simmons Cancer Center, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., 75235-8593, Dallas, TX

    Kenji Sugio, Arvind K. Virmani, Yosuke Kishimoto & Adi F. Gazdar

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  1. Kenji Sugio
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  2. Kyle Molberg
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Sugio, K., Molberg, K., Albores-Saavedra, J. et al. K-ras mutations and allelic loss at 5q and 18q in the development of human pancreatic cancers. Int J Gastrointest Canc 21, 205–217 (1997). https://doi.org/10.1007/BF02821606

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  • DOI: https://doi.org/10.1007/BF02821606

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