title: LINE-1 hypomethylation is neither present in rectal aberrant crypt foci nor associated with field defect in sporadic colorectal neoplasia.
abstract: BACKGROUND
  Aberrant crypt foci (ACF) are considered the first identifiable preneoplastic lesion in colorectal cancer (CRC), and have been proposed as a potential biomarker for CRC risk. Global DNA hypomethylation is an early event in colorectal carcinogenesis, and long interspersed nuclear element-1 (LINE-1) methylation status is a well-known surrogate marker for genome-wide DNA methylation levels. Despite the gradual increase in DNA hypomethylation in the adenoma-carcinoma sequence, LINE-1 methylation in ACF has never been studied. Moreover, recent studies have reported a field defect for LINE-1 hypomethylation, suggesting that LINE-1 methylation status in normal mucosa could be used to stratify CRC risk and tailor preventive strategies. Thus, we assessed LINE-1 status by pyrosequencing in rectal ACF and paired normal colorectal mucosa from individuals with sporadic colon cancer (CC) (n = 35) or adenoma (n = 42), and from healthy controls (n = 70).
  
  
  RESULTS
  Compared with normal mucosa, LINE-1 in ACF were hypermethylated across all groups (P < 0.0001). Furthermore, LINE-1 methylation status in normal colorectal mucosa was independent of the presence of adenoma or CC (P = 0.1072), and did not differ depending on the distance to the adenoma or CC. Interestingly, when we compared the LINE-1 methylation status in normal mucosa from different segments of the colorectum, we found higher hypomethylation in the rectum compared with the descending colon (P < 0.0001).
  
  
  CONCLUSIONS
  Overall, our results suggest that global hypomethylation is not present in rectal ACF and argues against the existence of LINE-1 methylation field defect in sporadic colon cancer.
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Isabel
authors: I
authors: Quintanilla
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Maria
authors: M
authors: Lopez-Cerón
authors: Pathology Department, Centre de Diagnostic Biomèdic (CDB), Hospital Clínic, University of Barcelona and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Barcelona, Catalonia, Spain.
authors: Mireya
authors: M
authors: Jimeno
authors: Pathology Department, Centre de Diagnostic Biomèdic (CDB), Hospital Clínic, University of Barcelona and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Barcelona, Catalonia, Spain.
authors: Miriam
authors: M
authors: Cuatrecasas
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Jennifer
authors: J
authors: Muñoz
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Leticia
authors: L
authors: Moreira
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Sabela
authors: S
authors: Carballal
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Maria Liz
authors: ML
authors: Leoz
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Jordi
authors: J
authors: Camps
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Antoni
authors: A
authors: Castells
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Maria
authors: M
authors: Pellisé
authors: Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain.
authors: Francesc
authors: F
authors: Balaguer
keywords: Aberrant crypt foci; Colorectal cancer; LINE-1; Methylation; Prevention