Methylation levels of LINE-1 in primary lesion and matched metastatic lesions of colorectal cancer

• Published in: British journal of cancer Vol. 109; no. 2; pp. 408 - 415
• Main Authors: Murata, A, Baba, Y, Watanabe, M, Shigaki, H, Miyake, K, Ishimoto, T, Iwatsuki, M, Iwagami, S, Sakamoto, Y, Miyamoto, Y, Yoshida, N, Nosho, K, Baba, H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.07.2013; Nature Publishing Group
• Subjects: 631/208/176/1988; 692/53/2422; 692/699/67/1504/1885; 692/699/67/322; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Chemotherapy; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA Methylation; Drug Resistance; Epidemiology; Epigenetics; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Neoplastic; Genetic testing; Genomes; Humans; Liver; Liver Neoplasms - genetics; Liver Neoplasms - secondary; Long Interspersed Nucleotide Elements - genetics; Lymphatic Metastasis; Lymphatic system; Male; Matched-Pair Analysis; Medical prognosis; Medical sciences; Metastasis; Middle Aged; Models, Biological; Molecular Diagnostics; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Oncology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; United States > US; Japan; LINE-1; epigenetics; colorectal cancer; Rectal disease; Colorectal cancer; Malignant tumor; Metastasis; Colonic disease; Cancerology; Primary; Epigenetics; Digestive diseases; Intestinal disease; Advanced stage; Lesion; Methylation; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.289

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.