• 中國醫(yī)科大學附屬第一醫(yī)院普外科（沈陽 110001）;

目的　探討中國胰腺癌患者Ki-ras基因第12密碼子突變表型的特點及與西方國家胰腺癌的區(qū)別。方法　采用PCR擴增靶基因片段，Dot blot雜交的方法檢測59例中國胰腺癌患者標本中Ki-ras基因第12密碼子突變表型。利用Medline檢索相關(guān)西方國家文獻報道的胰腺癌患者Ki-ras基因第12密碼子突變表型，并與本組資料進行對比。結(jié)果　本組患者Ki-ras基因第12密碼子突變頻繁（76.3%）。與西方國家文獻報道的資料比較顯示，各國胰腺癌患者中Ki-ras基因第12密碼子突變頻率差異無統(tǒng)計學意義（P＞0.05），但突變的表型及第二堿基突變的轉(zhuǎn)換和顛換比的差異存在統(tǒng)計學意義（P＜0.05，P＜0.01，P＜0.001）。結(jié)論　Ki-ras基因第12密碼子突變在中國胰腺癌患者較頻繁，其突變表型在各國胰腺癌患者中可能存在差異。

引用本文： 董明,周建平,張浩,郭克建,田雨霖,董雨亭. 中國人與西方人胰腺癌組織中Ki-ras基因第12密碼子突變表型的比較△. 中國普外基礎(chǔ)與臨床雜志, 2006, 13(5): 524-528. doi: 復制

1. 　Hruban RH, van Mansfeld AD, Offerhaus GJ, et al. K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization [J]. Am J Pathol, 1993; 143(2)∶545.
2. 　Pellegata NS, Sessa F, Renault B, et al. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions [J]. Cancer Res, 1994; 54(6)∶1556.
3. 　Sugio K, Gazdar AF, Albores-Saavedra J, et al. High yields of K-ras mutations in intraductal papillary mucinous tumors and invasive adenocarcinomas induced by N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine in the pancreas of female Syrian hamsters [J]. Carcinogenesis, 1996; 17(2)∶303.
4. 　Scarpa A, Capelli P, Villaneuva A, et al. Pancreatic cancer in Europe: Ki-ras gene mutation pattern shows geographical differences [J]. Int J Cancer, 1994; 57(2)∶167.
5. 　Tada M, Ohashi M, Shiratori Y, et al. Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease [J]. Gastroenterology, 1996; 110(1)∶227.
6. 　 van Es JM, Polak MM, van den Berg FM, et al. Molecular markers for diagnostic cytology of neoplasms in the head region of the pancreas: mutation of K-ras and overexpression of the p53 protein product [J]. J Clin Pathol, 1995; 48(3)∶218.
7. 　Grunewald K, Lyons J, Frohlich A. High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas [J]. Int J Cancer, 1989; 43(6)∶1037.
8. 　Sobin LH, Wittekind CH Eds. TNM classification of malignant tu-mours [M]. New York: John Wiley and Sons, Inc, 1997∶87-90.
9. 　Neuman WL, Wasylyshyn ML, Jacoby R, et al. Evidence for a common molecular pathogenesis in colorectal, gastric, and pancreatic cancer [J]. Genes Chromosomes Cancer, 1991; 3(6)∶468.
10. 　Burmer GC, Rabinovitch PS, Loeb LA. Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma [J]. Environ Health Perspect, 1991; 93∶27.
11. 　Lemoine NR, Jain S, Hughes CM, et al. Ki-ras oncogene activation in preinvasive pancreatic cancer [J]. Gastroenterology, 1992; 102(1)∶230.
12. 　Mulcahy HE, Lyautey J, Lederrey C, et al. A prospective study of K-ras mutations in the plasma of pancreatic cancer patients [J]. Clin Cancer Res, 1998; 4(2)∶271.
13. 　Berrozpe G, Schaeffer J, Peinado MA, et al. Comparative analysis of mutations in the p53 and K-ras genes in pancreatic cancer [J]. nt J Cancer, 1994; 58(2)∶185.
14. 　Smit VT, Boot AJ, Smits AM, et al. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas [J]. ucleic Acids Res, 1988; 16(16)∶7773.
15. 　Goelz SE, Hamilton SR, Vogelstein B. et al. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue [J]. Biochem Biophys Res Commun, 1985; 130(1)∶118.
16. 　Tominaga S. Epidemiology of pancreatic cancer [J]. Gan To Kagaku Ryoho, 1992; 19(14)∶2297.
17. 　Nagata Y, Abe M, Motoshima K, et al. Frequent glycine-to-aspartic acid mutations at codon 12 of c-Ki-ras gene in human pancreatic cancer in Japanese [J]. Jpn J Cancer Res, 1990; 81(2)∶135.
18. 　Castells A, Puig P, Mora J, et al. K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance [J]. J Clin Oncol, 1999; 17(2)∶578.
19. 　Song MM, Nio Y, Dong M, et al. Comparison of K-ras point mutations at codon 12 and p21 expression in pancreatic cancer between Japanese and Chinese patients [J]. J Surg Oncol, 2000; 75(3)∶176.
20. 　Parada LF, Land H, Weinberg RA, et al. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation [J]. Nature, 1984; 312(5995)∶649.
21. 　Zambetti GP, Olson D, Labow M, et al. A mutant p53 protein is required for maintenance of the transformed phenotype in cells transformed with p53 plus ras cDNAs [J]. Proc Natl Acad Sci USA， 1992; 89(9)∶3952.
  1. 1. 　Hruban RH, van Mansfeld AD, Offerhaus GJ, et al. K-ras oncogene activation in adenocarcinoma of the human pancreas. A study of 82 carcinomas using a combination of mutant-enriched polymerase chain reaction analysis and allele-specific oligonucleotide hybridization [J]. Am J Pathol, 1993; 143(2)∶545.
  2. 2. 　Pellegata NS, Sessa F, Renault B, et al. K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions [J]. Cancer Res, 1994; 54(6)∶1556.
  3. 3. 　Sugio K, Gazdar AF, Albores-Saavedra J, et al. High yields of K-ras mutations in intraductal papillary mucinous tumors and invasive adenocarcinomas induced by N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine in the pancreas of female Syrian hamsters [J]. Carcinogenesis, 1996; 17(2)∶303.
  4. 4. 　Scarpa A, Capelli P, Villaneuva A, et al. Pancreatic cancer in Europe: Ki-ras gene mutation pattern shows geographical differences [J]. Int J Cancer, 1994; 57(2)∶167.
  5. 5. 　Tada M, Ohashi M, Shiratori Y, et al. Analysis of K-ras gene mutation in hyperplastic duct cells of the pancreas without pancreatic disease [J]. Gastroenterology, 1996; 110(1)∶227.
  6. 6. 　 van Es JM, Polak MM, van den Berg FM, et al. Molecular markers for diagnostic cytology of neoplasms in the head region of the pancreas: mutation of K-ras and overexpression of the p53 protein product [J]. J Clin Pathol, 1995; 48(3)∶218.
  7. 7. 　Grunewald K, Lyons J, Frohlich A. High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas [J]. Int J Cancer, 1989; 43(6)∶1037.
  8. 8. 　Sobin LH, Wittekind CH Eds. TNM classification of malignant tu-mours [M]. New York: John Wiley and Sons, Inc, 1997∶87-90.
  9. 9. 　Neuman WL, Wasylyshyn ML, Jacoby R, et al. Evidence for a common molecular pathogenesis in colorectal, gastric, and pancreatic cancer [J]. Genes Chromosomes Cancer, 1991; 3(6)∶468.
  10. 10. 　Burmer GC, Rabinovitch PS, Loeb LA. Frequency and spectrum of c-Ki-ras mutations in human sporadic colon carcinoma, carcinomas arising in ulcerative colitis, and pancreatic adenocarcinoma [J]. Environ Health Perspect, 1991; 93∶27.
  11. 11. 　Lemoine NR, Jain S, Hughes CM, et al. Ki-ras oncogene activation in preinvasive pancreatic cancer [J]. Gastroenterology, 1992; 102(1)∶230.
  12. 12. 　Mulcahy HE, Lyautey J, Lederrey C, et al. A prospective study of K-ras mutations in the plasma of pancreatic cancer patients [J]. Clin Cancer Res, 1998; 4(2)∶271.
  13. 13. 　Berrozpe G, Schaeffer J, Peinado MA, et al. Comparative analysis of mutations in the p53 and K-ras genes in pancreatic cancer [J]. nt J Cancer, 1994; 58(2)∶185.
  14. 14. 　Smit VT, Boot AJ, Smits AM, et al. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas [J]. ucleic Acids Res, 1988; 16(16)∶7773.
  15. 15. 　Goelz SE, Hamilton SR, Vogelstein B. et al. Purification of DNA from formaldehyde fixed and paraffin embedded human tissue [J]. Biochem Biophys Res Commun, 1985; 130(1)∶118.
  16. 16. 　Tominaga S. Epidemiology of pancreatic cancer [J]. Gan To Kagaku Ryoho, 1992; 19(14)∶2297.
  17. 17. 　Nagata Y, Abe M, Motoshima K, et al. Frequent glycine-to-aspartic acid mutations at codon 12 of c-Ki-ras gene in human pancreatic cancer in Japanese [J]. Jpn J Cancer Res, 1990; 81(2)∶135.
  18. 18. 　Castells A, Puig P, Mora J, et al. K-ras mutations in DNA extracted from the plasma of patients with pancreatic carcinoma: diagnostic utility and prognostic significance [J]. J Clin Oncol, 1999; 17(2)∶578.
  19. 19. 　Song MM, Nio Y, Dong M, et al. Comparison of K-ras point mutations at codon 12 and p21 expression in pancreatic cancer between Japanese and Chinese patients [J]. J Surg Oncol, 2000; 75(3)∶176.
  20. 20. 　Parada LF, Land H, Weinberg RA, et al. Cooperation between gene encoding p53 tumour antigen and ras in cellular transformation [J]. Nature, 1984; 312(5995)∶649.
  21. 21. 　Zambetti GP, Olson D, Labow M, et al. A mutant p53 protein is required for maintenance of the transformed phenotype in cells transformed with p53 plus ras cDNAs [J]. Proc Natl Acad Sci USA， 1992; 89(9)∶3952.