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Nucleic Acids Research Advance Access originally published online on September 6, 2008
Nucleic Acids Research 2008 36(17):5704-5712; doi:10.1093/nar/gkn571
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Nucleic Acids Research, 2008, Vol. 36, No. 17 5704-5712
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

LINE-1 methylation patterns of different loci in normal and cancerous cells

Chureerat Phokaew1, Supakit Kowudtitham1, Keskanya Subbalekha2, Shanop Shuangshoti3 and Apiwat Mutirangura4,*

1Inter-Department Program of BioMedical Sciences, Faculty of Graduate School, 2Department of Surgery, Faculty of Dentistry, 3Department of Pathology, Faculty of Medicine and 4Center for Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand

*To whom correspondence should be addressed. Tel: +662 256 4532; Fax: +662 254 1931; Email: mapiwat{at}chula.ac.th

Received June 3, 2008. Revised August 20, 2008. Accepted August 22, 2008.

This study evaluated methylation patterns of long interspersed nuclear element-1 (LINE-1) sequences from 17 loci in several cell types, including squamous cell cancer cell lines, normal oral epithelium (NOE), white blood cells and head and neck squamous cell cancers (HNSCC). Although sequences of each LINE-1 are homologous, LINE-1 methylation levels at each locus are different. Moreover, some loci demonstrate the different methylation levels between normal tissue types. Interestingly, in some chromosomal regions, wider ranges of LINE-1 methylation levels were observed. In cancerous cells, the methylation levels of most LINE-1 loci demonstrated a positive correlation with each other and with the genome-wide levels. Therefore, the loss of genome-wide methylation in cancerous cells occurs as a generalized process. However, different LINE-1 loci showed different incidences of HNSCC hypomethylation, which is a lower methylation level than NOE. Additionally, we report a closer direct association between two LINE-1s in different EPHA3 introns. Finally, hypermethylation of some LINE-1s can be found sporadically in cancer. In conclusion, even though the global hypomethylation process that occurs in cancerous cells can generally deplete LINE-1 methylation levels, LINE-1 methylation can be influenced differentially depending on where the particular sequences are located in the genome.


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