© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 11, 858-865,
June 6, 2001
© 2001 Oxford University Press
REPORT |
Detecting Colorectal Cancer in Stool With the Use of Multiple Genetic Targets
Affiliations of authors: S. M. Dong, L. Geng, K. Hibi, D. Sidransky (Division of Head and Neck Cancer Research, Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins Medical School), G. Traverso (The Johns Hopkins Oncology Center and Program in Human Genetics), S. N. Goodman, K. W. Kinzler (The Johns Hopkins Oncology Center), B. Vogelstein (Howard Hughes Medical Institute and The Johns Hopkins Oncology Center), The Johns Hopkins University, Baltimore, MD; C. Johnson, S. R. Hamilton, B. Levin, The University of Texas M. D. Anderson Cancer Center, Houston; R. Favis, F. Barany, Department of Microbiology, Cornell University, Ithaca, NY; M. D'Allessio, P. Paty, Memorial Sloan-Kettering Cancer Center, New York, NY; K. Boynton, A. Shuber, EXACT Laboratories, Inc., Maynard, MA; J. Jen, Division of Head and Neck Cancer Research, Department of Otolaryngology–Head and Neck Surgery, The Johns Hopkins Oncology Center, The Johns Hopkins Medical School, and Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD.
Correspondence to: Jin Jen, Ph.D., National Institutes of Health, Bldg. 41, Rm. D702, 41 Library Dr., Bethesda, MD 20892 (jenj{at}mail.nih.gov).
Background: Colorectal cancer cells are shed into the stool, providing a potential means for the early detection of the disease using noninvasive approaches. Our goal was to develop reliable, specific molecular genetic tests for the detection of colorectal cancer in stool samples. Methods: Stool DNA was isolated from paired stools and primary tumor samples from 51 colorectal cancer patients. Three genetic targets—TP53, BAT26, and K-RAS—were used to detect tumor-associated mutations in the stool prior to or without regard to the molecular analyses of the paired tumors. TP53 gene mutations were detected with a mismatch-ligation assay that detects nine common p53 gene mutations. Deletions within the BAT26 locus were detected by a modified solid-phase minisequencing method. Mutations in codons 12 and 13 of K-RAS were detected with a digital polymerase chain reaction-based method. Results: TP53 gene mutations were detected in the tumor DNA of 30 patients, all of whom had the identical TP53 mutation in their stools. Tumors from three patients contained a noninherited deletion at the BAT26 locus, and the same alterations were identified in these patients' stool specimens. Nineteen of 50 tumors tested had a K-RAS mutation; identical mutations were detected in the paired stool DNA samples from eight patients. In no case was a mutation found in stool that was not also present in the primary tumor. Thus, the three genetic markers together detected 36 (71%) of 51 patients (95% confidence interval [CI] = 56% to 83%) with colorectal cancer and 36 (92%) of 39 patients (95% CI = 79% to 98%) whose tumors had an alteration. Conclusion: We were able to detect the majority of colorectal cancers by analyzing stool DNA for just three genetic markers. Additional work is needed to determine the specificity of these genetic tests for detecting colorectal neoplasia in asymptomatic patients and to more precisely estimate the prevalence of the mutations and sensitivity of the assay.
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 Y. Kim, S. Lee, S. Park, H. Jeon, W. Lee, J. K. Kim, M. Cho, M. Kim, J. Lim, C. S. Kang, et al. Gastrointestinal Tract Cancer Screening Using Fecal Carcinoembryonic Antigen Ann. Clin. Lab. Sci., January 1, 2003; 33(1): 32 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 A Wagner, C Tops, J T Wijnen, K Zwinderman, C van der Meer, M Kets, M F Niermeijer, J G M Klijn, A Tibben, H F A Vasen, et al. Genetic testing in hereditary non-polyposis colorectal cancer families with a MSH2, MLH1, or MSH6 mutation J. Med. Genet., November 1, 2002; 39(11): 833 - 837. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kaur, Y. Zhang, W.-H. Liu, S. Tetradis, B. D. Price, and G. M. Makrigiorgos Ligation of a primer at a mutation: a method to detect low level mutations in DNA Mutagenesis, September 1, 2002; 17(5): 365 - 374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
A. B. Lowenfels Fecal occult blood testing as a screening procedure for colorectal cancer Ann. Onc., January 19, 2002; 13(1): 40 - 43. [Full Text] [PDF]
|
|
|
|
|
|
P. Autier Should organised faecal occult blood test screening be established? Ann. Onc., January 19, 2002; 13(1): 57 - 60. [Full Text] [PDF]
|
|
|
|
|
|
M. Widschwendter and P. A. Jones The Potential Prognostic, Predictive, and Therapeutic Values of DNA Methylation in Cancer : Commentary re: J. Kwong et al., Promoter Hypermethylation of Multiple Genes in Nasopharyngeal Carcinoma. Clin. Cancer Res., 8: 131-137, 2002, and H-Z. Zou et al., Detection of Aberrant p16 Methylation in the Serum of Colorectal Cancer Patients. Clin. Cancer Res., 8: 188-191, 2002. Clin. Cancer Res., January 1, 2002; 8(1): 17 - 21. [Full Text] [PDF]
|
|
|
|
 |
|
 Another Multitarget Molecular Stool Test for Colorectal Cancer Journal Watch Gastroenterology, August 15, 2001; 2001(815): 6 - 6. [Full Text]
|
|
|
|
|
|
W. Atkin and J. P. Martin Stool DNA-Based Colorectal Cancer Detection: Finding the Needle in the Haystack J Natl Cancer Inst, June 6, 2001; 93(11): 798 - 799. [Full Text] [PDF]
|
|