Detection of stool DNA mutations before and after treatment of colorectal neoplasia
β Scribed by Sapna Syngal; Elena Stoffel; Daniel Chung; Christopher Willett; David Schoetz; Paul Schroy; Deepa Jagadeesh; Kathleen Morel; Michael Ross
- Book ID
- 102104111
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 86 KB
- Volume
- 106
- Category
- Article
- ISSN
- 0008-543X
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β¦ Synopsis
Abstract
BACKGROUND
Whether stool DNA abnormalities arise solely from colorectal neoplastic lesions or are due to more pervasive field effects is not known. In the current study, the authors conducted a prospective multicenter study to evaluate the performance of stoolβbased DNA testing in a large cohort and to examine whether the findings before treatment persist after surgical resection and/or adjuvant therapy.
METHODS
Patients with newly diagnosed colorectal carcinoma or advanced adenomas (AA) provided stool samples before therapy, 1β3 months after surgical resection, and 6β9 months postresection. Stool samples were analyzed using the multitarget DNA assay panel (MTAP) consisting of 23 markers: 21 mutations in the p53, Kβras, and APC genes, a microsatellite instability marker (BATβ26), and the DNA integrity assay (DIA), a marker of loss of apoptosis.
RESULTS
Overall, 49 of 91 individuals (54%) tested positive with the MTAP test. The sensitivity of the MTAP test was 63% for invasive tumors compared with 26% for AA. Individuals whose lesions had a more advanced TNM stage or were located distal to the splenic flexure were significantly more likely to have a positive MTAP test. Of the 79 samples collected at 1β3 months after surgical resection of the neoplasm, 14 (18%) had a positive MTAP result, 12 of which were positive for DIA only. Of those collected at 6β9 months of followβup, 5 of 72 (7%) tested positive on the MTAP panel.
CONCLUSIONS
Although many samples collected 1β3 months after surgical resection of the colorectal neoplasm tested positive on the MTAP, most were negative by 6β9 months, indicating that stool DNA abnormalities disappear after treatment of the neoplastic lesions. Surgery and chemoradiation appear to induce transient DIA abnormalities that may be independent of the presence of neoplasia. Cancer 2006. Β© 2005 American Cancer Society.
π SIMILAR VOLUMES
In most cases the analysis of DNA mutations in presence of a high excess of wild type DNA fail because of the low sensitivity of the performed method for mutation detection. Here we describe the new high-sensitive and non-radioactive HD-PCR method (for HeteroDuplex-PCR). In opposite to the conventio