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. 1996 Mar;38(3):426–429. doi: 10.1136/gut.38.3.426

K-ras gene mutation in gall bladder carcinomas and dysplasia.

T Ajiki 1, T Fujimori 1, H Onoyama 1, M Yamamoto 1, S Kitazawa 1, S Maeda 1, Y Saitoh 1
PMCID: PMC1383074  PMID: 8675098

Abstract

Epithelial dysplasia of gall bladder is an important precancerous lesion of gall bladder carcinogenesis. To investigate the frequency of K-ras gene mutation in gall bladder carcinoma and dysplasia, K-ras codon 12 mutations were investigated by the polymerase chain reaction/restriction enzyme based method following direct sequencing. Mutation was detected in 59% (30 of 51) of gall bladder carcinomas, in 73% (8 of 11) of gall bladder dysplasia in gall stone cases, and in 0% of the normal gall bladder epithelium. There was, however, no correlation between K-ras mutation and clinicopathological factors of gall bladder carcinoma. K-ras gene mutation occurs even in gall bladder dysplasia at an incidence similar to that in carcinomas, suggesting that testing for K-ras gene mutation may prove useful as an adjunct to bile cytological or biopsy analysis.

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Selected References

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  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. Cerny W. L., Mangold K. A., Scarpelli D. G. K-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian golden hamster. Cancer Res. 1992 Aug 15;52(16):4507–4513. [PubMed] [Google Scholar]
  3. Chen J., Viola M. V. A method to detect ras point mutations in small subpopulations of cells. Anal Biochem. 1991 May 15;195(1):51–56. doi: 10.1016/0003-2697(91)90293-3. [DOI] [PubMed] [Google Scholar]
  4. Dowling G. P., Kelly J. K. The histogenesis of adenocarcinoma of the gallbladder. Cancer. 1986 Oct 15;58(8):1702–1708. doi: 10.1002/1097-0142(19861015)58:8<1702::aid-cncr2820580821>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  5. Imai M., Hoshi T., Ogawa K. K-ras codon 12 mutations in biliary tract tumors detected by polymerase chain reaction denaturing gradient gel electrophoresis. Cancer. 1994 Jun 1;73(11):2727–2733. doi: 10.1002/1097-0142(19940601)73:11<2727::aid-cncr2820731113>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Kihana T., Tsuda H., Hirota T., Shimosato Y., Sakamoto H., Terada M., Hirohashi S. Point mutation of c-Ki-ras oncogene in gastric adenoma and adenocarcinoma with tubular differentiation. Jpn J Cancer Res. 1991 Mar;82(3):308–314. doi: 10.1111/j.1349-7006.1991.tb01847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kimura W., Shimada H., Kuroda A., Morioka Y. Carcinoma of the gallbladder and extrahepatic bile duct in autopsy cases of the aged, with special reference to its relationship to gallstones. Am J Gastroenterol. 1989 Apr;84(4):386–390. [PubMed] [Google Scholar]
  9. Kozuka S., Tsubone N., Yasui A., Hachisuka K. Relation of adenoma to carcinoma in the gallbladder. Cancer. 1982 Nov 15;50(10):2226–2234. doi: 10.1002/1097-0142(19821115)50:10<2226::aid-cncr2820501043>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  10. Kubo K., Naoe T., Kiyoi H., Fukutani H., Kato Y., Oguri T., Yamamori S., Akatsuka Y., Kodera Y., Ohno R. Clonal analysis of multiple point mutations in the N-ras gene in patients with acute myeloid leukemia. Jpn J Cancer Res. 1993 Apr;84(4):379–387. doi: 10.1111/j.1349-7006.1993.tb00147.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Levi S., Urbano-Ispizua A., Gill R., Thomas D. M., Gilbertson J., Foster C., Marshall C. J. Multiple K-ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique. Cancer Res. 1991 Jul 1;51(13):3497–3502. [PubMed] [Google Scholar]
  12. Losi L., Benhattar J., Costa J. Stability of K-ras mutations throughout the natural history of human colorectal cancer. Eur J Cancer. 1992;28A(6-7):1115–1120. doi: 10.1016/0959-8049(92)90468-h. [DOI] [PubMed] [Google Scholar]
  13. Mariyama M., Kishi K., Nakamura K., Obata H., Nishimura S. Frequency and types of point mutation at the 12th codon of the c-Ki-ras gene found in pancreatic cancers from Japanese patients. Jpn J Cancer Res. 1989 Jul;80(7):622–626. doi: 10.1111/j.1349-7006.1989.tb01687.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sagawa H., Tazuma S., Kajiyama G. Protection against hydrophobic bile salt-induced cell membrane damage by liposomes and hydrophilic bile salts. Am J Physiol. 1993 May;264(5 Pt 1):G835–G839. doi: 10.1152/ajpgi.1993.264.5.G835. [DOI] [PubMed] [Google Scholar]
  15. Scarpa A., Capelli P., Villaneuva A., Zamboni G., Lluìs F., Accolla R., Mariuzzi G., Capellà G. Pancreatic cancer in Europe: Ki-ras gene mutation pattern shows geographical differences. Int J Cancer. 1994 Apr 15;57(2):167–171. doi: 10.1002/ijc.2910570206. [DOI] [PubMed] [Google Scholar]
  16. Tada M., Omata M., Ohto M. Analysis of ras gene mutations in human hepatic malignant tumors by polymerase chain reaction and direct sequencing. Cancer Res. 1990 Feb 15;50(4):1121–1124. [PubMed] [Google Scholar]
  17. Verlaan-de Vries M., Bogaard M. E., van den Elst H., van Boom J. H., van der Eb A. J., Bos J. L. A dot-blot screening procedure for mutated ras oncogenes using synthetic oligodeoxynucleotides. Gene. 1986;50(1-3):313–320. doi: 10.1016/0378-1119(86)90335-5. [DOI] [PubMed] [Google Scholar]
  18. Vogelstein B., Fearon E. R., Hamilton S. R., Kern S. E., Preisinger A. C., Leppert M., Nakamura Y., White R., Smits A. M., Bos J. L. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988 Sep 1;319(9):525–532. doi: 10.1056/NEJM198809013190901. [DOI] [PubMed] [Google Scholar]
  19. Watanabe M., Asaka M., Tanaka J., Kurosawa M., Kasai M., Miyazaki T. Point mutation of K-ras gene codon 12 in biliary tract tumors. Gastroenterology. 1994 Oct;107(4):1147–1153. doi: 10.1016/0016-5085(94)90240-2. [DOI] [PubMed] [Google Scholar]
  20. Yamagiwa H., Tomiyama H. Intestinal metaplasia-dysplasia-carcinoma sequence of the gallbladder. Acta Pathol Jpn. 1986 Jul;36(7):989–997. doi: 10.1111/j.1440-1827.1986.tb00209.x. [DOI] [PubMed] [Google Scholar]
  21. Yamaguchi K., Enjoji M. Carcinoma of the gallbladder. A clinicopathology of 103 patients and a newly proposed staging. Cancer. 1988 Oct 1;62(7):1425–1432. doi: 10.1002/1097-0142(19881001)62:7<1425::aid-cncr2820620730>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]

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