LINE-1 hypomethylation is neither present in rectal aberrant crypt foci nor associated with field defect in sporadic colorectal neoplasia

Clinical Epigenetics

Francesc Balaguer¹  Maria Pellisé¹  Antoni Castells¹  Jordi Camps¹  Maria Liz Leoz¹  Sabela Carballal¹  Leticia Moreira¹  Jennifer Muñoz¹  Miriam Cuatrecasas²  Mireya Jimeno²  Maria Lopez-Cerón¹  Isabel Quintanilla¹ 

[1] Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBEREHD), IDIBAPS, Barcelona, Catalonia, Spain;Pathology Department, Centre de Diagnostic Biomèdic (CDB), Hospital Clínic, University of Barcelona and Banc de Tumors-Biobanc Clinic-IDIBAPS-XBTC, Barcelona, Catalonia, Spain

关键词: Prevention;    Methylation;    LINE-1;    Aberrant crypt foci;    Colorectal cancer;   

Others  :  1092793
DOI  :  10.1186/1868-7083-6-24

 received in 2014-08-14, accepted in 2014-10-17,  发布年份 2014

【 摘 要 】

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).

Findings

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.

【 授权许可】

   
2014 Quintanilla et al.; licensee BioMed Central Ltd.

【 图 表 】

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