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. 1994 Aug;70(2):278–284. doi: 10.1038/bjc.1994.292

Diagnosis of pancreatic adenocarcinoma by polymerase chain reaction from pancreatic secretions.

L H Trümper 1, B Bürger 1, F von Bonin 1, A Hintze 1, G von Blohn 1, M Pfreundschuh 1, H Daus 1
PMCID: PMC2033495  PMID: 8054276

Abstract

As mutations at codon 12 of the Ki-ras oncogene have been shown to occur in 90% of pancreatic adenocarcinomas, a novel strategy for the detection of these mutations in pancreatic secretions obtained at routine endoscopies was developed. Ki-ras DNA was amplified and screened for the presence of mutations at codon 12 with a combination of different rapid, non-radioactive molecular biology techniques. Examination of DNA from cell lines and paraffin-embedded tumour samples was used to establish and test the strategy employed. Pancreatic secretions from 27 patients were examined for the presence of Ki-ras mutations. Mutations at codon 12 were detected in 16/16 secretions from patients with histologically confirmed carcinoma and from one patient with carcinoma of the bile duct. In six patients a mutation identical to the one found in the pancreatic secretions was also demonstrated in paraffin-embedded fine-needle biopsy or surgical samples. Of the remaining ten patients (who had pancreatitis or cholelithiasis) mutations were not found in nine. Ki-ras codon 12 mutation was identified in one of these patients however, and mucous cell hyperplasia of pancreatic ducts was found upon histological examination. These findings establish Ki-ras polymerase chain reaction from pancreatic secretions as a valuable new diagnostic procedure for the demonstration of malignant cells, possibly at an early stage of the disease.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Almoguera C., Shibata D., Forrester K., Martin J., Arnheim N., Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell. 1988 May 20;53(4):549–554. doi: 10.1016/0092-8674(88)90571-5. [DOI] [PubMed] [Google Scholar]
  2. Brisson-Noël A., Gicquel B., Lecossier D., Lévy-Frébault V., Nassif X., Hance A. J. Rapid diagnosis of tuberculosis by amplification of mycobacterial DNA in clinical samples. Lancet. 1989 Nov 4;2(8671):1069–1071. doi: 10.1016/s0140-6736(89)91082-9. [DOI] [PubMed] [Google Scholar]
  3. Kahn S. M., Jiang W., Culbertson T. A., Weinstein I. B., Williams G. M., Tomita N., Ronai Z. Rapid and sensitive nonradioactive detection of mutant K-ras genes via 'enriched' PCR amplification. Oncogene. 1991 Jun;6(6):1079–1083. [PubMed] [Google Scholar]
  4. Kahn S., Yamamoto F., Almoguera C., Winter E., Forrester K., Jordano J., Perucho M. The c-K-ras gene and human cancer (review). Anticancer Res. 1987 Jul-Aug;7(4A):639–652. [PubMed] [Google Scholar]
  5. Kerem E., Corey M., Kerem B. S., Rommens J., Markiewicz D., Levison H., Tsui L. C., Durie P. The relation between genotype and phenotype in cystic fibrosis--analysis of the most common mutation (delta F508). N Engl J Med. 1990 Nov 29;323(22):1517–1522. doi: 10.1056/NEJM199011293232203. [DOI] [PubMed] [Google Scholar]
  6. Laure F., Courgnaud V., Rouzioux C., Blanche S., Veber F., Burgard M., Jacomet C., Griscelli C., Brechot C. Detection of HIV1 DNA in infants and children by means of the polymerase chain reaction. Lancet. 1988 Sep 3;2(8610):538–541. doi: 10.1016/s0140-6736(88)92659-1. [DOI] [PubMed] [Google Scholar]
  7. Lowenfels A. B., Maisonneuve P., Cavallini G., Ammann R. W., Lankisch P. G., Andersen J. R., Dimagno E. P., Andrén-Sandberg A., Domellöf L. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N Engl J Med. 1993 May 20;328(20):1433–1437. doi: 10.1056/NEJM199305203282001. [DOI] [PubMed] [Google Scholar]
  8. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  9. Sidransky D., Tokino T., Hamilton S. R., Kinzler K. W., Levin B., Frost P., Vogelstein B. Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors. Science. 1992 Apr 3;256(5053):102–105. doi: 10.1126/science.1566048. [DOI] [PubMed] [Google Scholar]
  10. Tada M., Omata M., Kawai S., Saisho H., Ohto M., Saiki R. K., Sninsky J. J. Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res. 1993 Jun 1;53(11):2472–2474. [PubMed] [Google Scholar]
  11. Tada M., Omata M., Ohto M. Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma. Gastroenterology. 1991 Jan;100(1):233–238. doi: 10.1016/0016-5085(91)90606-l. [DOI] [PubMed] [Google Scholar]
  12. Warshaw A. L., Fernández-del Castillo C. Pancreatic carcinoma. N Engl J Med. 1992 Feb 13;326(7):455–465. doi: 10.1056/NEJM199202133260706. [DOI] [PubMed] [Google Scholar]
  13. Yanagisawa A., Ohtake K., Ohashi K., Hori M., Kitagawa T., Sugano H., Kato Y. Frequent c-Ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation. Cancer Res. 1993 Mar 1;53(5):953–956. [PubMed] [Google Scholar]

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