Methylation levels of LINE-1 in primary lesion and matched metastatic lesions of colorectal cancer |
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Authors: | A Murata Y Baba M Watanabe H Shigaki K Miyake T Ishimoto M Iwatsuki S Iwagami Y Sakamoto Y Miyamoto N Yoshida K Nosho H Baba |
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Institution: | 1.Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto 860-8556, Japan;2.First Department of Internal Medicine, Sapporo Medical University School of Medicine, S-1 W-16 Chuo-ku, Sapporo 60-8543, Japan |
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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. |
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Keywords: | LINE-1 colorectal cancer epigenetics |
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