Skip to main content
PMC home page
Gut logoLink to Gut
. 1993 Mar;34(3):392–396. doi: 10.1136/gut.34.3.392

High frequency of K-ras mutations in sporadic colorectal adenomas.

E A McLellan 1, R A Owen 1, K A Stepniewska 1, J P Sheffield 1, N R Lemoine 1
PMCID: PMC1374148  PMID: 8472989

Abstract

The frequency of activating mutations at codons 12 and 13 of the K-ras gene was investigated in 57 sporadic adenomas from 47 patients using the polymerase chain reaction and oligonucleotide hybridisation assay. Sixty eight per cent of the adenomas tested were positive for K-ras mutations. This high frequency, combined with the lack of a correlation between mutations and adenoma size, suggest that K-ras mutations occur earlier in the adenoma-carcinoma sequence than has previously been suggested. The high frequency observed in sporadic adenomas contrasts with the reported low frequency (18%) in adenomas from patients with familial adenomatous polyposis (FAP), suggesting a possible difference in the molecular genesis of FAP and non-FAP adenomas. Finally, it was found that adenomas from patients with a personal history of colorectal cancer were more likely to contain a K-ras mutation than those from patients with no such history. This is a new finding and worthy of further study.

Full text

PDF
392

Images in this article

394p394-a
on p.394

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ando M., Maruyama M., Oto M., Takemura K., Endo M., Yuasa Y. Higher frequency of point mutations in the c-K-ras 2 gene in human colorectal adenomas with severe atypia than in carcinomas. Jpn J Cancer Res. 1991 Mar;82(3):245–249. doi: 10.1111/j.1349-7006.1991.tb01836.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bell S. M., Kelly S. A., Hoyle J. A., Lewis F. A., Taylor G. R., Thompson H., Dixon M. F., Quirke P. c-Ki-ras gene mutations in dysplasia and carcinomas complicating ulcerative colitis. Br J Cancer. 1991 Jul;64(1):174–178. doi: 10.1038/bjc.1991.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bos J. L., Fearon E. R., Hamilton S. R., Verlaan-de Vries M., van Boom J. H., van der Eb A. J., Vogelstein B. Prevalence of ras gene mutations in human colorectal cancers. 1987 May 28-Jun 3Nature. 327(6120):293–297. doi: 10.1038/327293a0. [DOI] [PubMed] [Google Scholar]
  4. Burmer G. C., Levine D. S., Kulander B. G., Haggitt R. C., Rubin C. E., Rabinovitch P. S. c-Ki-ras mutations in chronic ulcerative colitis and sporadic colon carcinoma. Gastroenterology. 1990 Aug;99(2):416–420. doi: 10.1016/0016-5085(90)91024-z. [DOI] [PubMed] [Google Scholar]
  5. Burmer G. C., Loeb L. A. Mutations in the KRAS2 oncogene during progressive stages of human colon carcinoma. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2403–2407. doi: 10.1073/pnas.86.7.2403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen J., Compton C., Cheng E., Fromowitz F., Viola M. V. c-Ki-ras mutations in dysplastic fields and cancers in ulcerative colitis. Gastroenterology. 1992 Jun;102(6):1983–1987. doi: 10.1016/0016-5085(92)90323-q. [DOI] [PubMed] [Google Scholar]
  7. Delattre O., Olschwang S., Law D. J., Melot T., Remvikos Y., Salmon R. J., Sastre X., Validire P., Feinberg A. P., Thomas G. Multiple genetic alterations in distal and proximal colorectal cancer. Lancet. 1989 Aug 12;2(8659):353–356. doi: 10.1016/s0140-6736(89)90537-0. [DOI] [PubMed] [Google Scholar]
  8. Farr C. J., Marshall C. J., Easty D. J., Wright N. A., Powell S. C., Paraskeva C. A study of ras gene mutations in colonic adenomas from familial polyposis coli patients. Oncogene. 1988 Dec;3(6):673–678. [PubMed] [Google Scholar]
  9. Forrester K., Almoguera C., Han K., Grizzle W. E., Perucho M. Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. 1987 May 28-Jun 3Nature. 327(6120):298–303. doi: 10.1038/327298a0. [DOI] [PubMed] [Google Scholar]
  10. Halter S. A., Webb L., Rose J. Lack of ras mutations and prediction of long-term survival in carcinoma of the colon. Mod Pathol. 1992 Mar;5(2):131–134. [PubMed] [Google Scholar]
  11. Hayakumo T., Azuma T., Nakajima M., Yasuda K., Cho E., Mukai H., Mizuma Y., Ashihara T., Mizuno S., Hirano S. [Prevalence of K-ras gene mutations in human colorectal cancers]. Nihon Shokakibyo Gakkai Zasshi. 1991 Aug;88(8):1539–1544. [PubMed] [Google Scholar]
  12. Hill M. J. Cancer of the large bowel: human carcinogenesis. Br J Surg. 1985 Sep;72 (Suppl):S37–S39. doi: 10.1002/bjs.1800721322. [DOI] [PubMed] [Google Scholar]
  13. Jackson D. P., Lewis F. A., Taylor G. R., Boylston A. W., Quirke P. Tissue extraction of DNA and RNA and analysis by the polymerase chain reaction. J Clin Pathol. 1990 Jun;43(6):499–504. doi: 10.1136/jcp.43.6.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jiang W., Kahn S. M., Guillem J. G., Lu S. H., Weinstein I. B. Rapid detection of ras oncogenes in human tumors: applications to colon, esophageal, and gastric cancer. Oncogene. 1989 Jul;4(7):923–928. [PubMed] [Google Scholar]
  15. Laurent-Puig P., Olschwang S., Delattre O., Validire P., Melot T., Mosseri V., Salmon R. J., Thomas G. Association of Ki-ras mutation with differentiation and tumor-formation pathways in colorectal carcinoma. Int J Cancer. 1991 Sep 9;49(2):220–223. doi: 10.1002/ijc.2910490213. [DOI] [PubMed] [Google Scholar]
  16. Miyaki M., Seki M., Okamoto M., Yamanaka A., Maeda Y., Tanaka K., Kikuchi R., Iwama T., Ikeuchi T., Tonomura A. Genetic changes and histopathological types in colorectal tumors from patients with familial adenomatous polyposis. Cancer Res. 1990 Nov 15;50(22):7166–7173. [PubMed] [Google Scholar]
  17. Nagata Y., Abe M., Kobayashi K., Yoshida K., Ishibashi T., Naoe T., Nakayama E., Shiku H. Glycine to aspartic acid mutations at codon 13 of the c-Ki-ras gene in human gastrointestinal cancers. Cancer Res. 1990 Feb 1;50(3):480–482. [PubMed] [Google Scholar]
  18. Oliva M. R., Cabrera T., Esquivias J., Perez-Ayala M., Redondo M., Ruiz-Cabello F., Garrido F. K-ras mutations (codon 12) are not involved in down-regulation of MHC class-I genes in colon carcinomas. Int J Cancer. 1990 Sep 15;46(3):426–431. doi: 10.1002/ijc.2910460317. [DOI] [PubMed] [Google Scholar]
  19. Oudejans J. J., Slebos R. J., Zoetmulder F. A., Mooi W. J., Rodenhuis S. Differential activation of ras genes by point mutation in human colon cancer with metastases to either lung or liver. Int J Cancer. 1991 Dec 2;49(6):875–879. doi: 10.1002/ijc.2910490613. [DOI] [PubMed] [Google Scholar]
  20. Sasaki M., Sugio K., Sasazuki T. K-ras activation in colorectal tumors from patients with familial polyposis coli. Cancer. 1990 Jun 1;65(11):2576–2579. doi: 10.1002/1097-0142(19900601)65:11<2576::aid-cncr2820651130>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  21. Shaw P., Tardy S., Benito E., Obrador A., Costa J. Occurrence of Ki-ras and p53 mutations in primary colorectal tumors. Oncogene. 1991 Nov;6(11):2121–2128. [PubMed] [Google Scholar]
  22. 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]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES