title: Methylation levels of LINE-1 in primary lesion and matched metastatic lesions of colorectal cancer.
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.
  
  
  CONCLUSIONS
  Alteration of LINE-1 methylation level may occur in early CRC tumorigenesis, and the LINE-1 methylation level is relatively stable during CRC progression.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Kumamoto City, Kumamoto, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Murata
authors.forename: Y
authors.initials: Y
authors.lastname: Baba
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: H
authors.initials: H
authors.lastname: Shigaki
authors.forename: K
authors.initials: K
authors.lastname: Miyake
authors.forename: T
authors.initials: T
authors.lastname: Ishimoto
authors.forename: M
authors.initials: M
authors.lastname: Iwatsuki
authors.forename: S
authors.initials: S
authors.lastname: Iwagami
authors.forename: Y
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: N
authors.initials: N
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Nosho
authors.forename: H
authors.initials: H
authors.lastname: Baba
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D008954:Models, Biological