Faecal DNA testing for colon cancer

The surgical cure rate for colon cancer is high (up to 90%) when it is detected in its earliest stages, but the popularity of current invasive screening methods is low. Screening for cancer-associated, aberrant DNA methylation in patient blood and faeces has been validated as a potential, non-invasive method of early detection for this disease. However, the currently available markers are not very sensitive or specific. Wei-Dong Chen and colleagues have therefore investigated expanding the repertoire of available methylated-DNA markers for colon cancer by using the methylation status of the non-expressed vimentin gene, VIM.

VIM has a dense region of CpG dinucleotides in and around its first exon, which are targets for DNA methylation. The authors designed primers to assay this region of DNA for methylation and showed that even though VIM is transcriptionally silent in normal mucosal epithelial cells, this DNA region was normally unmethylated. However, in all the cancer cell lines tested this region of VIM was 100% methylated.

In most matched pairs of normal and tumour tissue samples from colon cancer patients, methylation of VIM exon 1 was specifically present in the cancerous tissues, and was found in both early- and late-stage tumours. Furthermore, the VIM-methylation assay could detect colon cancer with a clinical sensitivity of 46% and a specificity of 90%, which compares favourably with the parameters for methylation assays of other individual genes. An existing panel of DNA biomarkers for colon cancer has a combined sensitivity of 52% and a specificity of 94%, so adding this assay to the panel could improve these parameters. The authors will therefore begin using the assay in a multicentre trial that is aimed at identifying an optimal panel of biomarkers for colon cancer detection through faecal DNA testing. ORIGINAL RESEARCH PAPER Chen, W. D. et al. Detection in fecal DNA of colon cancer-specific methylation of the nonexpressed vimentin gene. J. Natl Cancer Inst. 97, 1124–1132 (2005)

Cancer immunization success

The proteins p53 and KRAS are commonly mutated in cancer, and David Carbone and colleagues have now shown that this can be exploited in cancer immunotherapy.

Short peptides were synthesized to correspond to the individual mutations in p53 or KRAS of 39 patients with varying stages of cancer. Mononuclear cells from the peripheral blood of each patient were then pulsed with these peptides, irradiated and returned to the patients intravenously. No toxicity was observed and the results were positive: 26% of the patients produced cytotoxic T lymphocytes (CTLs) against the mutant proteins and 42% of patients showed positive interferon-γ (IFNγ) responses after vaccination. Median survival times of 393 versus 98 days for a positive versus a negative CTL response, and 470 versus 88 days for a positive versus negative IFNγ response were also seen. So, custom-made peptide vaccination is a feasible, non-toxic method of cancer immunotherapy that is associated with an increase in survival. ORIGINAL RESEARCH PAPER Carbone, D. P. et al. Immunization with mutant p53- and K-ras-derived peptides in cancer patients: immune response and clinical outcome. J. Clin. Oncol. 23, 5099–5107 (2005)