Comparative Study on Mutations at Codon 12 of Ki-ras Gene Between Chinese and Western Patients with Pancreatic Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

DONG Ming , ZHOU Jianping , ZHANG Hao , GUO Kejian , TIAN Yulin , DONG Yuting.

Department of Surgery, The First Affiliated Hospital, China Medical University, Shenyang 110001, China;

Corresponding author：

Keywords：

Pancreatic cancerKi-ras geneEpidemiology

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【Abstract】　Objective　To explore the features of Ki-ras mutations at codon 12 in Chinese patients of pancreatic cancer and to compare these features with those in Western countries. Methods　Fifty-nine samples were collected during operations for pancreatic adenocarcinoma in our hospital from December 1989 to November 1997. The patients, age ranged from 30 to 73 years 〔(55.5±10.4) years〕,with 38 males and 21 female. TNM staging of the patients: stage Ⅰ(n=4); stage Ⅱ(n=8), stage Ⅲ(n=42),stage Ⅳ(n=5). PCR was used to amplify target gene and Dot blot hybridization for detecting Ki-ras mutations at codon 12 was performed in fifty-nine specimens of Chinese pancreatic cancer. The data of Ki-ras mutations at codon 12 from Western countries were gotten by Medline system. Results　Ki-ras mutation at codon 12 was detected in 76.3% of the patients in this group. The frequency of double mutation of Ki-ras at codon 12 in this group (15.6%) was highest than that in western countries. Our results were compared with those reported in Western countries. The results suggested that there were the significant differences in the substitution of Ki-ras mutations at codon 12 and in the ratio of transition to transversion in pancreatic cancer among various countries. Conclusion　Ki-ras mutations at codon 12 is frequent in Chinese pancreatic cancer, and a gene component to pancreatic cancer may be different among various countries. In addition, the effect of Ki-ras mutations at codon 12 on prognosis of patients with pancreatic cancer is different in various countries.

Citation： DONG Ming,ZHOU Jianping,ZHANG Hao,GUO Kejian,TIAN Yulin,DONG Yuting.. Comparative Study on Mutations at Codon 12 of Ki-ras Gene Between Chinese and Western Patients with Pancreatic Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2006, 13(5): 524-528. doi: Copy

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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.
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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. 　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.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Comparative Study on Mutations at Codon 12 of Ki-ras Gene Between Chinese and Western Patients with Pancreatic Cancer

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