Journal
GASTROENTEROLOGY
Volume 135, Issue 2, Pages 489-498Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2008.05.039
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Funding
- Howard Hughes Medical Institute Funding Source: Medline
- NCI NIH HHS [R01 CA129825, R37 CA057345, P50 CA062924-090012, R37 CA043460-26, CA129825, CA43460, R37 CA043460, R37 CA057345-15, P50 CA062924-140017, P50 CA062924-08S30010, P50 CA062924, CA62924, R01 CA057345, CA57345, R37 CA057345-17] Funding Source: Medline
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Background & Aims: Somatic mutations provide uniquely specific markers for the early detection of neoplasia that can be detected in DNA purified from plasma or stool of patients with colorectal cancer. The primary purpose of the present investigation was to determine the parameters that were critical for detecting mutations using a quantitative assay. A secondary purpose was to compare the results of plasma and stool DNA testing using the same technology. Methods: We examined DNA purified from the stool of 25 patients with colorectal cancers before surgery. In 16 of these cases, plasma samples also were available. Mutations in stool or plasma were assessed with an improved version of the BEAMing technology. Results: Of the 25 stool DNA samples analyzed, 23 (92%) contained mutations that were present in the corresponding tumors from the same patients. In contrast, only 8 of the 16 (50%) plasma DNA samples analyzed had detectable levels of mutated DNA. We found that the DNA fragments containing mutations in both stool and plasma DNA typically were smaller than 150 bases in size. The sensitivity of the new method was superior to a widely used technique for detecting mutations, using single base extension and sequencing, when assessed on the same samples (92% vs 60%; P = .008, exact McNemar test). Conclusion : When assessed with sufficiently sensitive methods, mutant DNA fragments are detectable in the stool of more than 90% of colorectal. cancer patients. DNA purified from stool provides a better template for mutation testing than plasma.
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