Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia

Graham P. Lidgard, Michael J. Domanico, Janelle J. Bruinsma, James Light, Zubin D. Gagrat, Rebecca L. Oldham-Haltom, Keith D. Fourrier, Hatim Allawi, Tracy C. Yab, William R. Taylor, Julie A. Simonson, Mary Devens, Russell I. Heigh, David A. Ahlquist, Barry M. Berger

Research output: Contribution to journalArticle

80 Scopus citations


Background & Aims: Colorectal cancer (CRC) and advanced precancers can be detected noninvasively by analyses of exfoliated DNA markers and hemoglobin in stool. Practical and cost-effective application of a stool DNA-based (sDNA) test for general CRC screening requires high levels of accuracy and high-capacity throughput. We optimized an automated sDNA assay and evaluated its clinical performance. Methods: In a blinded, multicenter, case-control study, we collected stools from 459 asymptomatic patients before screening or surveillance colonoscopies and from 544 referred patients. Cases included CRC (n= 93), advanced adenoma (AA) (n= 84), or sessile serrated adenoma ≥1 cm (SSA) (n= 30); controls included nonadvanced polyps (n= 155) or no colonic lesions (n=641). Samples were analyzed by using an automated multi-target sDNA assay to measure β-actin (a marker of total human DNA), mutant KRAS, aberrantly methylated BMP3 and NDRG4, and fecal hemoglobin. Data were analyzed by a logistic algorithm to categorize patients as positive or negative for advanced colorectal neoplasia (CRC, advanced adenoma, and/or SSA ≥1 cm). Results: At 90% specificity, sDNA analysis identified individuals with CRC with 98% sensitivity. Its sensitivity for stage I cancer was 95%, for stage II cancer it was 100%, for stage III cancer it was 96%, for stage IV cancer it was 100%, and for stages I-III cancers it was 97% (nonsignificant Pvalue). Its sensitivity for advanced precancers (AA and SSA) ≥1 cm was 57%, for >2 cm it was 73%, and for >3 cm it was 83%. The assay detected AA with high-grade dysplasia with 83% sensitivity. Conclusions: We developed an automated, multi-target sDNA assay that detects CRC and premalignant lesions with levels of accuracy previously demonstrated with a manual process. This automated high-throughput system could be a widely accessible noninvasive approach to general CRC screening.

Original languageEnglish (US)
Pages (from-to)1313-1318
Number of pages6
JournalClinical Gastroenterology and Hepatology
Issue number10
StatePublished - Oct 1 2013


  • BMP3
  • Colon Cancer
  • Early Detection
  • NDRG4
  • QuARTS

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Lidgard, G. P., Domanico, M. J., Bruinsma, J. J., Light, J., Gagrat, Z. D., Oldham-Haltom, R. L., Fourrier, K. D., Allawi, H., Yab, T. C., Taylor, W. R., Simonson, J. A., Devens, M., Heigh, R. I., Ahlquist, D. A., & Berger, B. M. (2013). Clinical performance of an automated stool DNA assay for detection of colorectal neoplasia. Clinical Gastroenterology and Hepatology, 11(10), 1313-1318.