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Detection of Pancreatic Carcinoma (Diagnostic Value of K-ras Mutations in Circulating DNA from Serum)

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Abstract

Somatic activating mutations at codon 12 of theK-ras gene are present in the majority of exocrinepancreatic cancers and occur early in tumorgenesis. Theaim of this study was to test the feasibility of using a mutated K-ras gene from the serum as apotential tumor marker for detection of exocrinepancreatic carcinoma. Codon 12 K-ras mutations wereexamined in DNA extracted from the sera of 20 patients with pancreatic carcinomas, six patients withchronic pancreatitis, and five healthy individuals.K-ras gene mutations at codon 12 were detected in thesera of 14 of 20 patients with pancreatic carcinoma and in none of the six patients with chronicpancreatitis, or in the five healthy controls. Elevationof either CA19-9 or K-ras mutation was detected in 19/20patients. These results suggest that K-ras abnormalities in serum could be used as apotential tumor marker in patients with a pancreaticlesion. The absence of K-ras mutations in serum andpresence of CA19-9 in the normal range make thediagnosis of pancreatic cancer unlikely.

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REFERENCES

  1. Warsaw AL, Castillo CF: Pancreatic carcinoma. N Engl J Med 326:455–465, 1993

    Google Scholar 

  2. Niederau C, Grendfll JH. Diagnosis of pancreatic carcinoma. Pancreas 7:66–86, 1993

    Google Scholar 

  3. Mackie CR, Moosa AR, Go VLW, Noble G, Sizemore G, Cooper MJ, Wood RAB, Hall AW, Waldmann T, Gelder F, Rubenstein AH: Prospective evaluation of some candidate tumor markers in the diagnosis of pancreatic cancer. Dig Dis Sci 25:161–172, 1980

    Google Scholar 

  4. Schmiege l W: Tumor markers in pancreatic cancer-current concepts. Hepatogastroenterology 36:446–449, 1989

    Google Scholar 

  5. Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-rasgenes. Cell 53:549–553, 1988

    Google Scholar 

  6. Grunewald K, Lyons J, Frohlich A: High frequency of Ki-ras codon mutations in pancreatic adenocarcinomas. Int J Cancer 43:1037–1041, 1989

    Google Scholar 

  7. Smit VTHB, Boot AJ, Smits AMM, Fleuren GJ, Cornelisse CJ, Bos JL: K-ras codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res 16:7773–7782, 1988

    Google Scholar 

  8. Bos JL: Ras oncogene in human cancer: A review. Cancer Res 49:4682–4689, 1989

    Google Scholar 

  9. Almoguera C, Shibara D, Forrester K, Martin J, Amheim N, Perucho M: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:449–534, 1988

    Google Scholar 

  10. Villanueva A, Reyes G, Cuatrecasas M, Martinez A, Erill N, Lerma E, Farre A, Lluis F, Capella G: Diagnostic utility of K-ras mutations in fine-needle aspirates of pancreatic masses. Gastroenterology 110:1587–1594, 1996

    Google Scholar 

  11. Shibata D, Almoguera C, Forreter K, Duntz J, Martin SE, Cosgrove MM, Perucho M, Amheiim N: Detection of K-ras mutations in fine needle aspirates from human pancreatic cancer. Cancer Res 50:1279–1283, 1990

    Google Scholar 

  12. Tada M, Omata M, Ohto M: Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma. Gastroenterology 100:233–238, 1991

    Google Scholar 

  13. Urban T, Ticci S, Grange JD, Lacaave R, Boudghene F, Breittmayer F, Languille O, Roland J, Bernaudin IF: Detection of c-Ki-ras mutations by PCR/RFLP analysis and diagnosis of pancre atic adenocarcinomas. J Natl Cancer Inst 85:1978–1980,1993

    Google Scholar 

  14. Apple SK, Hecht RJ, Novak JM, Nieberg RK, Rosenthal DL, Grody WW: Polymerase chain reaction-based K-ras mutation detection of pancreatic adenocarcinoma in routine cytology smears. Am J Clin Pathol 105:321–326, 1996

    Google Scholar 

  15. Kondo H, Sugano K, Fukayama N, Kyogoku A, Nose H, Shimada K, Ohkura H, Ohtsu A, Yoshida S, Shimosato Y: Detection of point mutations in the K-ras oncogene at codon 12 in pure pancreatic juice for diagnosis of pancreatic carcinoma. Cancer 73:1589–1594, 1994

    Google Scholar 

  16. Lee JG, Leung JW, Cotton PB, Layfield LJ, Mannon PJ: Diagnostic utility of K-ras mutational analysis on bile obtained by endoscopic re trograde cholangio-pancreatography. Gastrointest Endosc 42:317–320, 1995

    Google Scholar 

  17. Iguchi H, Sugano K, Fukayama N, OhKura H, Sadamoto K, Ohkoshi K, Seo Y, Tomoda H, Funakoshi A, Wakasugi H: Analysis of Ki-ras codon 12 mutations in the duodenal juice of patients with pancreatic cancer. Gastroenterology 110:221–226, 1996

    Google Scholar 

  18. Tada M, Omata M, Kawai S, Ohto M, Saiki RK, Sninsky JJ: Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res 54:2472–2474, 1993

    Google Scholar 

  19. Watanabe H, Sawabu N, Ohta H, Wakabayashi T: Identification of K-ras oncogene mutations in the pure pancreatic juice of patients with ductal pancreatic cancers. Jpn J Cancer Res 84:961–965, 1993

    Google Scholar 

  20. Watanabe H, Sawabu N, Songur Y, Yamakawa O, Satomura Y, Ohta H, Motoo Y, Okita T, Wakabayashi T: Detection of K-ras point mutations at codon 12 in pure pancreatic juice for the diagnosis of pancreatic cancer by PCR-RFLP analysis. Pancreas 12:18–24, 1996

    Google Scholar 

  21. Kondo H, Sugano K, Fukayama N, Hosokawa K, Ohtsu A, Mukai K, Yoshida S: Detection of K-ras gene mutations at codon in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas. Cancer 79:900–905,1997

    Google Scholar 

  22. Furuya N, Kawa S, Akamatsu T, Furihata K: Long-term follow-up of patients with chronic pancreatitis and K-ras gene mutation detected in pancreatic juice. Gastroenterology 113:593–598, 1997

    Google Scholar 

  23. Tada M, Ohasi M, Shiratori Y, Okudaira T, Komatsu Y, Kawabe T, Yoshida H, Mochinami R, Kishi K, Omata M: Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease. Gastroenterology 110:227–231, 1996

    Google Scholar 

  24. 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 pancre as suffering from chronic inflammation. Cancer Res 53:953–956, 1993

    Google Scholar 

  25. Stroun M, Anker P, Maurice P, Lyautey J, Ledderey C, Beljanski M: Neoplastic characteristics of the DNA found in the plasma of cancer patients. Oncology 46:318–322, 1989

    Google Scholar 

  26. Shapiro B, Chakrabarry M, Cohn EM, Leon SA: Determination of circulating DNA levels in patients with benign or malignant gastrointestinal disease. Cancer 51:2116–2120, 1983

    Google Scholar 

  27. Dennin RH: DNA of free and complexed origin in human plasma: Concentration and length distribution. Klin Wochenschr 37:451–456, 1979

    Google Scholar 

  28. Klemp P, Meyers OL, Harley EH: Measurement of plasma DNA by a physiochemical method: Reliance in SLE. Ann Rheum Dis 40:593–599, 1981

    Google Scholar 

  29. Levi S, Urbano-Ispizua A, Gill R, Thomas DM, Gilbertson J, Foster C, Marshall CJ: Multiple K-ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique. Cancer Res 51:3497–3502, 1991

    Google Scholar 

  30. Anker P, Lefort F, Vasioukhin V, Lyautey J, Lederrey C, Chen XQ, Stroun M, Mulcahy HE, Farthing MJG: K-ras mutations are found in DNA extracted from the plasma of patients with colorectal cancer. Gastroenterology 112:1114–1120, 1997

    Google Scholar 

  31. Sorenson GD, Pribish DM, Valone FH, Memoli VA, Bzik DJ, Yao SL: Soluble normal and mutated DNA sequences from single-copy genes in human blood. Cance r Epidemiol Biomarkers Prev 3:67–71, 1994

    Google Scholar 

  32. Yamada T, Nakamori S, Ohzato H, Ohshima S, Aoki T, Higaki N, Sugimoto K, Akagi K, Fujiwara Y, Nishisho I, Sakon M, Gotoh M, Monden M: Detection of K-ras mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features. Clin Cancer Res 4(6):1527–1532, 1998

    Google Scholar 

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Theodor, L., Melzer, E., Sologov, M. et al. Detection of Pancreatic Carcinoma (Diagnostic Value of K-ras Mutations in Circulating DNA from Serum). Dig Dis Sci 44, 2014–2019 (1999). https://doi.org/10.1023/A:1026618317716

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