Abstract
We previously found p16 promoter methylation in DNA in the sera of 13 colorectal cancer patients out of 44 (30%) whose tumor DNA exhibited the methylation, using methylation‐specific PCR (MSP). To examine whether the cancer detection rate could be improved by using a different tumor marker, we examined the K‐ras status in 90 colorectal cancer patients using a mismatch ligation assay. Among the 31 patients showing K‐ras gene mutations in their tumors, the same mutations were observed in serum DNA of 11 patients (35%). Among the 90 patients, 63 showed tumors positive for K‐ras mutation or p16 promoter methylation, or both, and 22 had serum DNA positive for one or both. K‐ras mutation was found even in serum DNA of patients with Dukes A cancer, suggesting that colorectal cancer might be detected even in patients without symptoms by using this ligation assay.
Keywords: K‐ras, Colorectal cancer, Mismatch ligation assay
Full Text
The Full Text of this article is available as a PDF (43.9 KB).
REFERENCES
- 1.Cancer Facts & Figures 2000 ” ( 2000. ). American Cancer Society; , Atlanta , GA . [Google Scholar]
- 2. ) Esteller , M. , Sanchez‐Cespedes , M. , Rosell , R. , Sidransky , D. , Baylin , S. B. and Herman , J. G.Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non‐small cell lung cancer patients . Cancer Res. , 59 , 67 – 70 ( 1999. ). [PubMed] [Google Scholar]
- 3. ) Wong , I. H. , Lo , Y. M. , Zhang , J. , Liew , C. T. , Ng , M. H. , Wong , N. , Lai , P. B. , Lau , W. Y. , Hjelm , N. M. and Johnson , P. J.Detection of aberrant p16 methylation in the plasma and serum of liver cancer patients . Cancer Res. , 59 , 71 – 73 ( 1999. ). [PubMed] [Google Scholar]
- 4. ) Losas , S. L. , Koch , W. , da CostaCarvalho , M. G. , Wu , L. , Califano , J. , Westra , W. , Jen , J. and Sidransky , D.Promoter hypermethylation patterns of p16, O6‐methylguanine‐DNA‐methyltransferase, and death‐associated protein kinase in tumors and saliva of head and neck cancer patients . Cancer Res. , 61 , 939 – 942 ( 2001. ). [PubMed] [Google Scholar]
- 5. ) Sanchez‐Cespedes , M. , Esteller , M. , Wu , L. , Nawroz‐Danish , H. , Yoo , G. H. , Koch , W. M. , Jen , J. , Herman , J. G. and Sidransky , D.Gene promoter hypermethylation in tumors and serum of head and neck cancer patients . Cancer Res. , 60 , 892 – 895 ( 2000. ). [PubMed] [Google Scholar]
- 6. ) Chim , C. S. , Liang , R. , Tam , C. Y. and Kwong , Y. L.Methylation of p15 and p16 genes in acute promyelocytic leukemia: potential diagnostic and prognostic significance . J. Clin. Oncol. , 19 , 2033 – 2040 ( 2001. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Nakayama , H. , Hibi , K. , Taguchi , M. , Takase , T. , Yamazaki , T. , Kasai , Y. , Ito , K. , Akiyama , S. and Nakao , A.Molecular detection of p16 promoter methylation in the serum of colorectal cancer patients . Cancer Lett. ( 2002. ), in press . [DOI] [PubMed] [Google Scholar]
- 8. ) Sidransky , D.Circulating DNA: what we know and what we need to learn . Ann. NY Acad. Sci. , 906 , 1 – 4 ( 2000. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Hibi , K. , Robinson , C. R. , Booker , S. , Wu , L. , Hamilton , S. R. , Sidransky , D. and Jen , J.Molecular detection of genetic alterations in the serum of colorectal cancer patients . Cancer Res. , 58 , 1405 – 1407 ( 1998. ). [PubMed] [Google Scholar]
- 10. ) Sidransky , D. , Tokino , T. , Hamilton , S. R. , Kinzler , K. W. , Levin , B. , Frost , P. and Vogelstein , B.Identification of ras oncogene mutations in the stool of patients with curable colorectal tumors . Science , 256 , 102 – 105 ( 1992. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Boss , J. L. , Fearon , E. R. , Hamilton , S. R. , Vries , M. V. , Boom , J. H. and Vogelstein , B.Prevalence of ras gene mutations in human colorectal cancers . Nature , 327 , 293 – 297 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Vogelstein , B. , Fearon , E. R. , Hamilton , S. R. , Kern , S. E. , Preisinger , A. C. , Leppert , M. , Nakamura , Y. , White , R. , Smits , A. M. and Bos , J. L.Genetic alterations during colorectal‐tumor development . N. Engl. J. Med. , 319 , 525 – 532 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Kopreski , M. S. , Benko , F. A. , Kwee , C. , Leitzel , K. E. , Eskander , E. , Lipton , A. and Gocke , C. D.Detection of mutant K‐ras DNA in plasma or serum of patients with colorectal cancer . Br. J. Cancer , 76 , 1293 – 1299 ( 1997. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. ) Anker , P. , Lefort , F. , Vasioukhin , V. , Lyautey , J. , Lederrey , C. , Chen , X. Q. , Stroun , M. , Mulcahy , H. E. and Farthing , M. J.K‐ras mutations are found in DNA extracted from the plasma of patients with colorectal cancer . Gastroenterology , 112 , 1114 – 1120 ( 1997. ). [DOI] [PubMed] [Google Scholar]
- 15. ) de Kok , J. B. , van Solinge , W. W. , Ruers , T. J. , Roelofs , R. W. , van Muijen , G. N. , Willems , J. L. and Swinkels , D. W.Detection of tumour DNA in serum of colorectal cancer patients . Scand. J. Clin. Lab. Invest. , 57 , 601 – 604 ( 1997. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Traverse , G. , Shuber , A. , Olsson , L. , Levin , B. , Johnson , C. , Hamilton , S. R. , Boynton , K. , Kinzler , K. W. and Vogelstein , B.Detection of proximal colorectal cancers through analysis of faecal DNA . Lancet , 359 , 403 – 404 ( 2002. ). [DOI] [PubMed] [Google Scholar]
