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

Kenji Sugio, Kyle Molberg, Jorge Albores-Saavedra, Arvind K. Virmani, Yosuke Kishimoto, Adi F. Gazdar

Research output: Contribution to journalArticle

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Abstract

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. K-ras mutations occur early in the pathogenesis of pancreatic adenocarcinoma. Mutations were identified in multiple preneoplastic foci associated with all six cases in which ras 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. 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. Evidence for a "second hit" in the ras 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. In contrast to ras mutations, limited data suggest that loss of heterozygosity (LOH) at 5q and 18q are relatively late events.

Original languageEnglish (US)
Pages (from-to)205-217
Number of pages13
JournalInternational Journal of Gastrointestinal Cancer
Volume21
Issue number3
DOIs
StatePublished - Jun 1997

Fingerprint

Loss of Heterozygosity
Human Development
Pancreatic Neoplasms
Mutation
Hyperplasia
Pancreatic Ductal Carcinoma
Alleles
Neoplasms
ras Genes
Early Diagnosis
Adenocarcinoma
Epithelium

Keywords

  • 18q
  • 5q
  • K-ras
  • pancreatic cancer
  • preneoplastic lesions

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Endocrinology

Cite this

K-ras mutations and allelic loss at 5q and 18q in the development of human pancreatic cancers. / Sugio, Kenji; Molberg, Kyle; Albores-Saavedra, Jorge; Virmani, Arvind K.; Kishimoto, Yosuke; Gazdar, Adi F.

In: International Journal of Gastrointestinal Cancer, Vol. 21, No. 3, 06.1997, p. 205-217.

Research output: Contribution to journalArticle

Sugio, Kenji ; Molberg, Kyle ; Albores-Saavedra, Jorge ; Virmani, Arvind K. ; Kishimoto, Yosuke ; Gazdar, Adi F. / K-ras mutations and allelic loss at 5q and 18q in the development of human pancreatic cancers. In: International Journal of Gastrointestinal Cancer. 1997 ; Vol. 21, No. 3. pp. 205-217.
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N2 - 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. K-ras mutations occur early in the pathogenesis of pancreatic adenocarcinoma. Mutations were identified in multiple preneoplastic foci associated with all six cases in which ras 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. 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. Evidence for a "second hit" in the ras 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. In contrast to ras mutations, limited data suggest that loss of heterozygosity (LOH) at 5q and 18q are relatively late events.

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