Background & Aims: Evaluation of molecular alterations in fecal DNA is a potential, noninvasive, alternative tool for the detection of colorectal cancer. We analyzed a large panel of molecular alterations involved in tumor transformation and progression to define their single diagnostic contribution in terms of sensitivity, cost, and time required to carry out the different tests. Methods: DNA was analyzed in stool from 38 healthy individuals and in paired stools and primary lesions from 56 patients with colorectal cancer. p53 exons 5-8, K-ras exons 1-2, four fragments of adenomatous polyposis coli (APC) exon 15, and 5 microsatellite loci were analyzed. Moreover, DNA amplification was evaluated for 4 exons of both p53 and APC. Results: K-ras (34%) and p53 (34%) mutations were the most frequent alterations in tumors, followed by microsatellite instability (13%) and APC mutations (13%). The most frequent event in stool was DNA amplification (51%), followed by alterations of K-ras (11%), p53 and microsatellite instability (6%), and APC (2%). K-ras and p53 gene mutations increased the capacity of DNA amplification to detect tumor cells by 8%. Conclusions: K-ras and p53 gene mutations were the most frequent alterations observed in stool from patients with colorectal cancer, but DNA amplification was even more frequent, being present in more than half of patients. If these preliminary results are confirmed in a prospective study on a larger case series, this approach could be used for noninvasive colon cancer diagnosis in screening programs.
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