Background: A variety of tumor-related DNA has been detected in the plasma and serum of cancer patients, including RAS, the BCL2-IgH transgene, and p53. It is not known whether the APC gene, which is frequently mutated in colorectal cancer (CRC), can be identified in the plasma of CRC patients. Similarly, it is unknown whether another tumor suppressor gene altered in CRC, p53, is detectable in people with precursor lesions to CRC.
Materials and methods: The plasma of 240 colonoscopy patients was tested for mutations at two frequently altered sites (codons 175 and 248). A restriction enzyme-mediated enrichment assay was used to detect these mutants. We also tested tumor tissue from 8 patients with CRC for mutations in the mutation cluster region of the APC gene using direct DNA sequencing. Corresponding plasma from any positive patient was then similarly sequenced.
Results: Three plasma p53 mutations were identified. Two of these patients had adenomas at biopsy, and 1 had a hyperplastic polyp. All were tested for the same p53 mutations, and 1 of the adenomas was positive. One of the 8 CRC patients had a 5-base-pair deletion in the cancer and the same deletion was detectable in that patient's plasma, although at an amount that we estimate at 1-5% of the total APC DNA present.
Conclusions: APC mutations are detectable in the plasma of CRC patients. p53 mutants are detectable in the plasma of colorectal adenoma patients. These may have important implications for cancer screening and diagnosis in the large intestine and suggest that all malignant and premalignant DNA alterations from the colon are identifiable in the blood.