Detecting colorectal cancer in stool with the use of multiple genetic targets Journal Article
| Authors: | Dong, S. M.; Traverso, G.; Johnson, C.; Geng, L.; Favis, R.; Boynton, K.; Hibi, K.; Goodman, S. N.; D'alessio, M.; Paty, P.; Hamilton, S. R.; Sidransky, D.; Barany, F.; Levin, B.; Shuber, A.; Kinzler, K. W.; Vogelstein, B.; Jen, J. |
| Article Title: | Detecting colorectal cancer in stool with the use of multiple genetic targets |
| Abstract: | 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. |
| Keywords: | adult; controlled study; aged; middle aged; gene mutation; gene sequence; major clinical study; gene deletion; mutation; sequence deletion; cancer patient; molecular genetics; neoplasm staging; sensitivity and specificity; genetic analysis; polymerase chain reaction; colorectal cancer; reproducibility of results; gene targeting; disease association; prevalence; colonic neoplasms; gene locus; protein p53; assay; colorectal neoplasms; symptom; dna; early diagnosis; microsatellite instability; cancer cell; reliability; oncogene k ras; genes, ras; codon; dna determination; feces; non invasive measurement; germ-line mutation; marker gene; genetic markers; feces analysis; genes, p53; sample; inheritance; humans; human; male; female; priority journal; article |
| Journal Title: | JNCI: Journal of the National Cancer Institute |
| Volume: | 93 |
| Issue: | 11 |
| ISSN: | 0027-8874 |
| Publisher: | Oxford University Press |
| Date Published: | 2001-06-06 |
| Start Page: | 858 |
| End Page: | 865 |
| Language: | English |
| PUBMED: | 11390535 |
| PROVIDER: | scopus |
| DOI: | 10.1093/jnci/93.11.858 |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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