DNA methylation predicts recurrence from resected stage III proximal colon cancer
Article first published online: 18 NOV 2010
Copyright © 2010 American Cancer Society
Volume 117, Issue 9, pages 1847–1854, 1 May 2011
How to Cite
Ahn, J. B., Chung, W. B., Maeda, O., Shin, S. J., Kim, H. S., Chung, H. C., Kim, N. K. and Issa, J.-P. J. (2011), DNA methylation predicts recurrence from resected stage III proximal colon cancer. Cancer, 117: 1847–1854. doi: 10.1002/cncr.25737
- Issue published online: 19 APR 2011
- Article first published online: 18 NOV 2010
- Manuscript Accepted: 27 SEP 2010
- Manuscript Revised: 18 SEP 2010
- Manuscript Received: 7 JUL 2010
- colon cancer;
- CpG island methylator phenotype;
- methylation biomarker
In colorectal cancer (CRC), DNA methylation anomalies define distinct subgroups termed CpG island methylator phenotype 1 (CIMP1), CIMP2, and CIMP-negative. The role of this classification in predicting recurrence and disease-free survival (DFS) in resected stage III CRC was evaluated.
Sporadic cancers from 161 patients were analyzed. Bisulfite pyrosequencing was used to examine the methylation of 2 global DNA methylation markers (LINE-1, Alu) and 9 loci (MINT1, MINT2, MINT31, P16, hMLH1, P14, SFRP1, SFRP2, and WNT5A). Mutations in BRAF and KRAS were assayed.
Gene hypermethylation clustered in discrete groups of patients, indicating the presence of CIMP. K-means clustering analysis identified 3 discrete subgroups: CIMP1 (n = 22, 13.7%), associated with proximal location and BRAF mutations; CIMP2 (n = 40, 24.8%), associated with KRAS mutations; and CIMP-negative (n = 99, 61.5%), associated with distal location. In proximal CRC, CIMP1 was correlated with a higher recurrence rate (53% for CIMP1, 18% for CIMP2, and 26% for CIMP-negative) and a worse DFS (P = .015). Also in proximal CRC, LINE-1 methylation was lower in patients whose cancer recurred compared with those whose cancer did not recur (P = .049). In multivariate analysis, CIMP1 and low LINE1 methylation were independent prognostic factors for DFS in proximal CRC (P = .008 for classification by K-means clustering analysis; P = .040 for LINE-1 methylation status).
DNA methylation is a useful biomarker of recurrence in resected stage III proximal but not distal CRC. However, as the number of CIMP1 cases was small in distal CRC, further study is required to validate our findings. Cancer 2011. © 2010 American Cancer Society.