Summary
In order to clarify whether the detection of a point mutation in the c-Ki-ras gene at codon 12 in tumor tissues can assist in predicting the tumor’s biological grade of malignancy, two types of tumors were investigated; one was called “carcinoma in the pancreatic head region,” and the other was intraductal mucin-hypersecreting neoplasm of the pancreas (IMHN). Dot hybridization and a modified PCR technique developed by Haliassos et al. were employed. Among 16 cases of tumors in the pancreatic head region, the point mutation was detected with a high frequency only in pancreatic ductal cell carcinomas (five out of six cases, 83.3%), but was not detected in extrahepatic bile duct carcinomas (0/5) or in ampullary carcinomas (0/5). In pancreatic ductal cell carcinomas, no relation was found between the occurrence of the point mutation and the histological type of the tumor. Among 20 cases of IMHNs, the point mutation was found in 11 cases (55%). No relation was found between the occurrence of the mutation and the size of IMHNs. However, as the grade of cell atypia increased, the frequency of the mutation tended to become higher. These results suggest that detection of this point mutation might be useful for distinguishing pancreatic ductal cell carcinoma from those of other origins in the pancreatic head region, and for the determination of the histopathological grade of malignancy in IMHNs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Almoguera C, Shibata D, Forrester R, Martin J, Perucho M. Most human carcinoma of exocrine pancreas contain mutantc-R-ras genes.Cell 1988; 53: 549–554.
Tada M, Yokosuka, O, Omata M, Ohto M, Isono K. Analysis ofras gene mutation in biliary and pancreatic tumors by polymerase chain reaction and direct sequencing.Cancer 1990; 66: 930–935.
Smit VTHB, Boot AJ, Smits AA, Fluren GJ, Cornelisse CJ, Bos JL. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas.Nucleic Acid Res 1988; 16: 7773–7782.
Grüneward R, Lyons J, Fröhlich A, Feichtinger H, Weger RA, Schwab G, Janssen JWG, Bartram CR. High frequency of K-ras codon 12 mutation in pancreatic adenocarcinomas.Int J Cancer 1989; 43: 1037–1041.
Nagata Y, Abe M, Motoshima R, Nakayama E, Shiku H. Frequent Glycine-to-aspartic acid mutations at codon, 12 of c-Ki-ras gene in human pancreatic cancer in Japanese.Jpn J Cancer Res 1990; 81: 135–140
Satoh K, Sawai T, Shimosegawa T, Koizumi M, Yamazaki T, Mochizuki F, Toyota T. Point mutation of c-k-ras in mucin-producing cystic tumor of the pancreas.Nippon shyokakibyo gakkai zasshi (in Japanese) 1991; 88: 2795–2803.
Stork P, Loda M, Bosari S, Wiley B, Poppenhusen R, Wolfe H. Detection of K-ras mutations in pancreatic and hepatic neoplasms by non-isotopic mismatched polymerase chain reaction.Oncogene 1991; 6: 857–862.
Rickaert F, Cremer M, Devière J, Lambilliotte JP, Shröder S, Wurbs D, Klöppel G. Intraductal mucin-hypersecreting neoplasms of the pancreas: A clinicopathologic study of eight patients.Gastroenterology 1991; 101: 512–519.
Itai Y, Kokubo T, Atomi Y, Kuroda A, Haraguchi Y, Terano A. Mucin-hypersecreting carcinoma of the pancreas.Radiology 1987; 165: 51–55
Itai Y, Ohhashi R, Nagai H, Murakami Y, Kokubo T, Makita K, Ohtomo K. “Ductectatic” mucinous cystadenoma and cystadenocarcinoma of the pancreas.Radiology 1986; 161: 697–700.
Basid C, Bernard JP, Sarles H, Payan MJ, Sahel J. Mucinous ductal ectasia of pancreas: a premalignant disease and cause of obstructive pancreatitis.Pancreas 1991; 6: 15–22.
Kozuka S, Sassa R, Taki T, Masamoto K, Nagasawa S, Saga S, Hasegawa B, Takeuchi M. Relation of pancreatic duct hyperplasia to carcinoma.Cancer 1979; 43: 1418–1428.
Wright DK, Manos MM. Sample preparation from paraffin-embedded tissues, inPCR Protocols: a Guide to Methods and Applications. Academic Press, New York, 1990, 153–158.
Verlaan-de Vries M, Bogaad, ME, Elst H, Boom JH, Eb AJ, Bos JL. A dot-blot screening procedure for mutated ras oncogenes using synthetic oligodeoxynucleotides.Gene 1986; 313–320.
Haliassos A, Chomel JC, Grandjouan S, Kruh J, Kaplan JC, Kitzis A. Detection of minority point mutations by modified PCR technique: a new approach for sensitive diagnosis of tumor-progression markers.Nucleic Acid Res 1989; 8093–8099.
Tada M, Omata M, Ohto M.Ras gene mutations in intraductal papillary neoplasms of the pancreas. Analysis in five cases.Cancer 1991; 67: 634–637.
Morohoshi T, Kanda M, Asanuma R, Klöppel GL. Intraductal papillary neoplasm of the pancreas: A clinicopathologic study of six patients.Cancer 1989; 64: 1329–1335.
Lemoine NR, Jain S, Hughes CM, Staddon SL, Maillet B, Hall PA, Klöppel G. Ki-ras oncogene activation in preinvasive pancreatic cancer.Gastroenterology 1992; 102: 230–236.
Yanagisawa A, Kato Y, Ohtake K, Kitagawa O, Ohashi K, Hori M, Takagi K, Sugano H. C-Ki-ras point mutation in ductectatic-type mucinous cystic neoplasms of the pancreas.Jpn J Cancer Res 1991; 82: 1057–1060.
Barbacid M.ras Genes.Annu Rev Biochem 1987; 56: 779–827.
Bos JL. Theras gene family and human carcinogesis.Mutant Res 1988; 195: 255–271.
Bos JL.ras Oncogene in Human Cancer: A Review.Cancer Res 1989; 49: 4682–4689.
Forrester K, Almoguera C, Han K, Grizzle WE, Perucho M. Detection of high incidence of k-ras oncogenes during human colon tumorigenesis.Nature 1987; 327: 293–303.
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AMM, Bos JL. Genetic alterations during colorectal-tumor development.N Engl J Med 1988; 319: 525–532.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Satoh, K., Sawai, T., Shimosegawa, T. et al. The point mutation of c-Ki-ras at codon 12 in carcinoma of the pancreatic head region and in intraductal mucin-hypersecreting neoplasma of the pancreas. Int J Pancreatol 14, 135–143 (1993). https://doi.org/10.1007/BF02786119
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02786119