TY - JOUR
T1 - High Detection Rates of Colorectal Neoplasia by Stool DNA Testing With a Novel Digital Melt Curve Assay
AU - Zou, Hongzhi
AU - Taylor, William R.
AU - Harrington, Jonathan J.
AU - Hussain, Fareeda Taher Nazer
AU - Cao, Xiaoming
AU - Loprinzi, Charles L.
AU - Levine, Theodore R.
AU - Rex, Douglas K.
AU - Ahnen, Dennis
AU - Knigge, Kandice L.
AU - Lance, Peter
AU - Jiang, Xuan
AU - Smith, David I.
AU - Ahlquist, David A.
N1 - Funding Information:
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.
PY - 2009/2
Y1 - 2009/2
N2 - Background & Aims: Current stool DNA tests identify about half of individuals with colorectal cancers and miss most individuals with advanced adenomas. We developed a digital melt curve (DMC) assay to quantify low-abundance mutations in stool samples for detection of colorectal neoplasms and compared this test with other approaches. Methods: We combined a melt curve assay with digital polymerase chain reaction and validated the quantitative range. We then evaluated its ability to detect neoplasms in 2 clinical studies. In study I, stool samples from patients with colorectal tumors with known mutations (KRAS, APC, BRAF, TP53) were assayed. In study II, archived stool samples from patients with advanced adenomas containing known KRAS mutations were assayed, along with controls. Results were compared with those from the stool DNA test PreGenPlus (Exact Sciences, Marlborough, MA), Hemoccult, and HemoccultSensa (both Beckman-Coulter, Fullerton, CA). Results: The DMC assay detected samples in which only 0.1% of target genes were mutated. In study I, the DMC assay detected known mutations in 28 (90%) of 31 tumor samples and 6 (75%) of 8 advanced adenoma samples. In study II, the DMC assay detected 16 (59%) of 27 advanced adenoma samples that contained KRAS mutations, compared with 7% with the Hemoccult, 15% with the HemoccultSensa, and 26% with the PreGenPlus assays (P < .05 for each, compared with the DMC assay); specificities did not differ significantly. Conclusions: The DMC assay has a high level of sensitivity in detecting individuals with colon neoplasms and is better than current stool screening methods in detecting those with advanced adenomas. Further studies are indicated.
AB - Background & Aims: Current stool DNA tests identify about half of individuals with colorectal cancers and miss most individuals with advanced adenomas. We developed a digital melt curve (DMC) assay to quantify low-abundance mutations in stool samples for detection of colorectal neoplasms and compared this test with other approaches. Methods: We combined a melt curve assay with digital polymerase chain reaction and validated the quantitative range. We then evaluated its ability to detect neoplasms in 2 clinical studies. In study I, stool samples from patients with colorectal tumors with known mutations (KRAS, APC, BRAF, TP53) were assayed. In study II, archived stool samples from patients with advanced adenomas containing known KRAS mutations were assayed, along with controls. Results were compared with those from the stool DNA test PreGenPlus (Exact Sciences, Marlborough, MA), Hemoccult, and HemoccultSensa (both Beckman-Coulter, Fullerton, CA). Results: The DMC assay detected samples in which only 0.1% of target genes were mutated. In study I, the DMC assay detected known mutations in 28 (90%) of 31 tumor samples and 6 (75%) of 8 advanced adenoma samples. In study II, the DMC assay detected 16 (59%) of 27 advanced adenoma samples that contained KRAS mutations, compared with 7% with the Hemoccult, 15% with the HemoccultSensa, and 26% with the PreGenPlus assays (P < .05 for each, compared with the DMC assay); specificities did not differ significantly. Conclusions: The DMC assay has a high level of sensitivity in detecting individuals with colon neoplasms and is better than current stool screening methods in detecting those with advanced adenomas. Further studies are indicated.
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U2 - 10.1053/j.gastro.2008.10.023
DO - 10.1053/j.gastro.2008.10.023
M3 - Article
C2 - 19026650
AN - SCOPUS:58649111046
SN - 0016-5085
VL - 136
SP - 459
EP - 470
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -