Ontology highlight
ABSTRACT: Background
LINE-1 methylation level is a surrogate marker of global DNA methylation. LINE-1 methylation in primary colorectal cancers (CRCs) is highly variable and strongly associated with a poor prognosis. However, no study has examined LINE-1 methylation levels of metastatic CRCs in relation to prognosis or assessed the heterogeneity of LINE-1 methylation level within the primary CRCs.Methods
Pyrosequencing was used to quantify LINE-1 methylation level in 42 liver metastases, 26 matched primary tumours, and 6 matched lymph node (LN) metastases. KRAS, BRAF, and PIK3CA mutation status and microsatellite instability (MSI) status were also examined.Results
The distribution of LINE-1 methylation level in liver metastases was as follows: mean, 67.3; range, 37.1-90.1. Primary tumours showed LINE-1 methylation levels similar to those of matched liver and LN metastases. The difference in LINE-1 methylation level between superficial areas and invasive front areas was within 7.0 in all six cases evaluated. Prognostic impact of LINE-1 hypomethylation in liver metastases on overall survival was not observed. The concordance rate was 94% for KRAS, 100% for BRAF, 88% for PIK3CA, and 97% for MSI.Conclusion
Alteration of LINE-1 methylation level may occur in early CRC tumorigenesis, and the LINE-1 methylation level is relatively stable during CRC progression.
SUBMITTER: Murata A
PROVIDER: S-EPMC3721399 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Murata A A Baba Y Y Watanabe M M Shigaki H H Miyake K K Ishimoto T T Iwatsuki M M Iwagami S S Sakamoto Y Y Miyamoto Y Y Yoshida N N Nosho K K Baba H H
British journal of cancer 20130613 2
<h4>Background</h4>LINE-1 methylation level is a surrogate marker of global DNA methylation. LINE-1 methylation in primary colorectal cancers (CRCs) is highly variable and strongly associated with a poor prognosis. However, no study has examined LINE-1 methylation levels of metastatic CRCs in relation to prognosis or assessed the heterogeneity of LINE-1 methylation level within the primary CRCs.<h4>Methods</h4>Pyrosequencing was used to quantify LINE-1 methylation level in 42 liver metastases, 2 ...[more]