Gastroenterology
Volume 136, Issue 2 , Pages 459-470 , February 2009

High Detection Rates of Colorectal Neoplasia by Stool DNA Testing With a Novel Digital Melt Curve Assay

Data from this study were presented in part at Digestive Disease Week in San Diego, CA, May 20, 2008.

  • Hongzhi Zou

      Affiliations

    • Miles and Shirley Fiterman Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
    • Corresponding Author InformationAddress requests for reprints to: Hongzhi Zou, MD, PhD, or David A. Ahlquist, MD, Miles and Shirley Fiterman Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905. fax: (507) 255-6318
  • ,
  • William R. Taylor

      Affiliations

    • Miles and Shirley Fiterman Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Jonathan J. Harrington

      Affiliations

    • Miles and Shirley Fiterman Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Fareeda Taher Nazer Hussain

      Affiliations

    • Miles and Shirley Fiterman Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Xiaoming Cao

      Affiliations

    • Miles and Shirley Fiterman Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Charles L. Loprinzi

      Affiliations

    • Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota
  • ,
  • Theodore R. Levine

      Affiliations

    • Kaiser Permanente Medical Care Program, Oakland, California
  • ,
  • Douglas K. Rex

      Affiliations

    • Division of Gastroenterology, Indiana University School of Medicine, Indianapolis, Indiana
  • ,
  • Dennis Ahnen

      Affiliations

    • University of Colorado Health Sciences Center and Department of Veterans Affairs Medical Center, Denver, Colorado
  • ,
  • Kandice L. Knigge

      Affiliations

    • Division of Gastroenterology, Oregon Health & Science University, Portland, Oregon
  • ,
  • Peter Lance

      Affiliations

    • Arizona Cancer Center, Tucson, Arizona
  • ,
  • Xuan Jiang

      Affiliations

    • Division of Gastroenterology and Hepatology, People's Hospital, Peking University, Beijing, China
  • ,
  • David I. Smith

      Affiliations

    • Division of Experimental Pathology, Mayo Clinic, Rochester, Minnesota
  • ,
  • David A. Ahlquist

      Affiliations

    • Miles and Shirley Fiterman Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota

Received 19 June 2008 ,Accepted 9 October 2008.

References 

  1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96
  2. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood (Minnesota Colon Cancer Control Study). N Engl J Med. 1993;328:1365–1371
  3. Kronborg O, Fenger C, Olsen J, et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet. 1996;348:1467–1471
  4. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet. 1996;348:1472–1477
  5. Ahlquist DA, Wieand HS, Moertel CG, et al. Accuracy of fecal occult blood screening for colorectal neoplasia (A prospective study using Hemoccult and HemoQuant tests). JAMA. 1993;269:1262–1267
  6. Imperiale TF, Ransohoff DF, Itzkowitz SH, et al. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med. 2004;351:2704–2714
  7. Ahlquist DA, Sargent DJ, Loprinzi CL, et al. Stool DNA and occult blood testing for screen-detection of colorectal neoplasia: a prospective multi-center comparison. Ann Intern Med. 2008;149:441–450
  8. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy (The National Polyp Study Workgroup). N Engl J Med. 1993;329:1977–1981
  9. Schoen RE. Surveillance after positive and negative colonoscopy examinations: issues, yields, and use. Am J Gastroenterol. 2003;98:1237–1246
  10. Singh H, Turner D, Xue L, et al. Risk of developing colorectal cancer following a negative colonoscopy examination: evidence for a 10-year interval between colonoscopies. JAMA. 2006;295:2366–2373
  11. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58:130–160
  12. Ahlquist DA, Skoletsky JE, Boynton KA, et al. Colorectal cancer screening by detection of altered human DNA in stool: feasibility of a multitarget assay panel. Gastroenterology. 2000;119:1219–1227
  13. Osborn NK, Ahlquist DA. Stool screening for colorectal cancer: molecular approaches. Gastroenterology. 2005;128:192–206
  14. Coulet F, Blons H, Cabelguenne A, et al. Detection of plasma tumor DNA in head and neck squamous cell carcinoma by mi-crosatellite typing and p53 mutation analysis. Cancer Res. 2000;60:707–711
  15. Smith-Ravin J, England J, Talbot IC, et al. Detection of c-Ki-ras mutations in faecal samples from sporadic colorectal cancer patients. Gut. 1995;36:81–86
  16. Haug U, Hillebrand T, Bendzko P, et al. Mutant-enriched PCR and allele-specific hybridization reaction to detect K-ras mutations in stool DNA: high prevalence in a large sample of older adults. Clin Chem. 2007;53:787–790
  17. Berndt C, Haubold K, Wenger F, et al. K-ras mutations in stools and tissue samples from patients with malignant and nonmalignant pancreatic diseases. Clin Chem. 1998;44:2103–2107
  18. Soh J, Toyooka S, Ichihara S, et al. EGFR mutation status in pleural fluid predicts tumor responsiveness and resistance to gefitinib. Lung Cancer. 2007;56:445–448
  19. Traverso G, Shuber A, Levin B, et al. Detection of APC mutations in fecal DNA from patients with colorectal tumors. N Engl J Med. 2002;346:311–320
  20. Diehl F, Li M, He Y, et al. BEAMing: single-molecule PCR on microparticles in water-in-oil emulsions. Nat Methods. 2006;3:551–559
  21. Li M, Diehl F, Dressman D, et al. BEAMing up for detection and quantification of rare sequence variants. Nat Methods. 2006;3:95–97
  22. Diehl F, Li M, Dressman D, et al. Detection and quantification of mutations in the plasma of patients with colorectal tumors. Proc Natl Acad Sci U S A. 2005;102:16368–16373
  23. Wittwer CT, Reed GH, Gundry CN, et al. High-resolution genotyping by amplicon melting analysis using LCGreen. Clin Chem. 2003;49:853–860
  24. Montgomery J, Wittwer CT, Kent JO, et al. Scanning the cystic fibrosis transmembrane conductance regulator gene using high-resolution DNA melting analysis. Clin Chem. 2007;53:1891–1898
  25. Reed GH, Kent JO, Wittwer CT. High-resolution DNA melting analysis for simple and efficient molecular diagnostics. Pharmaco-genomics. 2007;8:597–608
  26. Vogelstein B, Kinzler KW. Digital PCR. Proc Natl Acad Sci U S A. 1999;96:9236–9241
  27. Traverso G, Shuber A, Olsson L, et al. Detection of proximal colorectal cancers through analysis of faecal DNA. Lancet. 2002;359:403–404
  28. Olson J, Whitney DH, Durkee K, et al. DNA stabilization is critical for maximizing performance of fecal DNA-based colorectal cancer tests. Diagn Mol Pathol. 2005;14:183–191
  29. Jiang X, Harrington JJ, Mahoney DW, et al. Detection of colorectal neoplasia by stool DNA testing: high discrimination with multi-marker quantification. Gastroenterology. 2008;134:A484
  30. Diehl F, Schmidt K, Durkee KH, et al. Analysis of mutations in DNA isolated from plasma and stool of colorectal cancer patients. Gastroenterology. 2008;135:489–498
  31. Sawyers C. Targeted cancer therapy. Nature. 2004;432:294–297
  32. Thomas RK, Nickerson E, Simons JF, et al. Sensitive mutation detection in heterogeneous cancer specimens by massively parallel picoliter reactor sequencing. Nat Med. 2006;12:852–855
  33. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129–2139
  34. Paez JG, Jänne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004;304:1497–1500
  35. Khambata-Ford S, Garrett CR, Meropol NJ, et al. Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007;25:3230–3237
  36. Lièvre A, Bachet JB, Boige V, et al. KRAS mutations as an independent prognostic factor in patients with advanced colorectal cancer treated with cetuximab. J Clin Oncol. 2008;26:374–379

 Supported by generous grants from Charles Oswald and from Eddie and Dana Gong. Patents on the digital melt curve methodology have been filed with the United States Patent Office by Drs Zou and Ahlquist.

 The authors disclose no conflicts.

PII: S0016-5085(08)01859-3

doi: 10.1053/j.gastro.2008.10.023

Gastroenterology
Volume 136, Issue 2 , Pages 459-470 , February 2009