Frequency and Spectrum of C-Ki-ras Mutations in Human Sporadic Colon Carcinoma, Carcinomas Arising in Ulcerative Colitis, and Pancreatic Adenocarcinoma

Overview

Journal Environ Health Perspect

Date 1991 Jun 1

PMID 1773797

Citations 15

Authors

G C Burmer

P S Rabinovitch

L A Loeb

Affiliations

Soon will be listed here.

Abstract

Sporadic colon carcinomas, carcinomas arising in chronic ulcerative colitis, and pancreatic adenocarcinomas have been analyzed for the presence of c-Ki-ras mutations by a combination of histological enrichment, cell sorting, polymerase chain reaction, and direct sequencing. Although 60% (37/61) of sporadic colon carcinomas contained mutations in codon 12, only 1 of 17 specimens of dysplasia or carcinoma from ulcerative colitis patients contained c-Ki-ras mutations, despite a high frequency of aneuploid tumors. In contrast, a higher percentage (16/20 = 80%) of pancreatic adenocarcinomas contained mutations in c-Ki-ras 2, despite a lower frequency of DNA aneuploidy in these neoplasms. Moreover, the spectrum of mutations differed between sporadic colon carcinoma, where the predominant mutation was a G to A transition, and pancreatic carcinomas, which predominantly contained G to C or T transversions. These results suggest that the etiology of ras mutations is different in these three human neoplasms.

Citing Articles

KRAS and TP53 mutations in inflammatory bowel disease-associated colorectal cancer: a meta-analysis.

Du L, Kim J, Shen J, Chen B, Dai N Oncotarget. 2017; 8(13):22175-22186.

PMID: 28077799 PMC: 5400656. DOI: 10.18632/oncotarget.14549.

Variation in KRAS driver substitution distributions between tumor types is determined by both mutation and natural selection.

Ostrow S, Simon E, Prinz E, Bick T, Shentzer T, Nagawkar S Sci Rep. 2016; 6:21927.

PMID: 26902163 PMC: 4763303. DOI: 10.1038/srep21927.

Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease-Associated Colorectal Cancers.

Robles A, Traverso G, Zhang M, Roberts N, Khan M, Joseph C Gastroenterology. 2016; 150(4):931-43.

PMID: 26764183 PMC: 5270616. DOI: 10.1053/j.gastro.2015.12.036.

Experimental animal models of pancreatic carcinogenesis for prevention studies and their relevance to human disease.

Takahashi M, Hori M, Mutoh M, Wakabayashi K, Nakagama H Cancers (Basel). 2013; 3(1):582-602.

PMID: 24212630 PMC: 3756378. DOI: 10.3390/cancers3010582.

RAS oncogenes: weaving a tumorigenic web.

Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D Nat Rev Cancer. 2011; 11(11):761-74.

PMID: 21993244 PMC: 3632399. DOI: 10.1038/nrc3106.

References

You M, Candrian U, Maronpot R, Stoner G, Anderson M . Activation of the Ki-ras protooncogene in spontaneously occurring and chemically induced lung tumors of the strain A mouse. Proc Natl Acad Sci U S A. 1989; 86(9):3070-4. PMC: 287066. DOI: 10.1073/pnas.86.9.3070. View

Nowell P . The clonal evolution of tumor cell populations. Science. 1976; 194(4260):23-8. DOI: 10.1126/science.959840. View

Burmer G, Rabinovitch P, Loeb L . Analysis of c-Ki-ras mutations in human colon carcinoma by cell sorting, polymerase chain reaction, and DNA sequencing. Cancer Res. 1989; 49(8):2141-6. View

Vogelstein B, Fearon E, Hamilton S, Kern S, Preisinger A, Leppert M . Genetic alterations during colorectal-tumor development. N Engl J Med. 1988; 319(9):525-32. DOI: 10.1056/NEJM198809013190901. View

Rodenhuis S, van de Wetering M, Mooi W, Evers S, van Zandwijk N, Bos J . Mutational activation of the K-ras oncogene. A possible pathogenetic factor in adenocarcinoma of the lung. N Engl J Med. 1987; 317(15):929-35. DOI: 10.1056/NEJM198710083171504. View

Quintanilla M, Brown K, Ramsden M, Balmain A . Carcinogen-specific mutation and amplification of Ha-ras during mouse skin carcinogenesis. Nature. 1986; 322(6074):78-80. DOI: 10.1038/322078a0. View

Wiseman R, Stowers S, Miller E, Anderson M, Miller J . Activating mutations of the c-Ha-ras protooncogene in chemically induced hepatomas of the male B6C3 F1 mouse. Proc Natl Acad Sci U S A. 1986; 83(16):5825-9. PMC: 386388. DOI: 10.1073/pnas.83.16.5825. View

Smit V, Boot A, Smits A, Fleuren G, Cornelisse C, Bos J . KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas. Nucleic Acids Res. 1988; 16(16):7773-82. PMC: 338489. DOI: 10.1093/nar/16.16.7773. View

Rodenhuis S, Slebos R, Boot A, Evers S, Mooi W, Wagenaar S . Incidence and possible clinical significance of K-ras oncogene activation in adenocarcinoma of the human lung. Cancer Res. 1988; 48(20):5738-41. View

10.

Isbell G, Levin B . Ulcerative colitis and colon cancer. Gastroenterol Clin North Am. 1988; 17(4):773-91. View

11.

Topal M . DNA repair, oncogenes and carcinogenesis. Carcinogenesis. 1988; 9(5):691-6. DOI: 10.1093/carcin/9.5.691. View

12.

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; 53(4):549-54. DOI: 10.1016/0092-8674(88)90571-5. View

13.

Forrester K, Almoguera C, Han K, Grizzle W, Perucho M . Detection of high incidence of K-ras oncogenes during human colon tumorigenesis. Nature. 1987; 327(6120):298-303. DOI: 10.1038/327298a0. View

14.

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; 80(7):622-6. PMC: 5917815. DOI: 10.1111/j.1349-7006.1989.tb01687.x. View

15.

Loeb L . Endogenous carcinogenesis: molecular oncology into the twenty-first century--presidential address. Cancer Res. 1989; 49(20):5489-96. View

16.

Grunewald K, Lyons J, Frohlich A, Feichtinger H, Weger R, Schwab G . High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas. Int J Cancer. 1989; 43(6):1037-41. DOI: 10.1002/ijc.2910430614. View

17.

Burmer G, Loeb L . Mutations in the KRAS2 oncogene during progressive stages of human colon carcinoma. Proc Natl Acad Sci U S A. 1989; 86(7):2403-7. PMC: 286921. DOI: 10.1073/pnas.86.7.2403. View

18.

Gyde S, Prior P, Allan R, Stevens A, Jewell D, TRUELOVE S . Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres. Gut. 1988; 29(2):206-17. PMC: 1433302. DOI: 10.1136/gut.29.2.206. View

19.

Barbacid M . ras genes. Annu Rev Biochem. 1987; 56:779-827. DOI: 10.1146/annurev.bi.56.070187.004023. View

20.

Nowell P . Mechanisms of tumor progression. Cancer Res. 1986; 46(5):2203-7. View