LINE-1 hypomethylation in familial and sporadic cancer

被引:0
作者
Walter Pavicic
Emmi I. Joensuu
Taina Nieminen
Päivi Peltomäki
机构
[1] University of Helsinki,Department of Medical Genetics, Haartman Institute
来源
Journal of Molecular Medicine | 2012年 / 90卷
关键词
LINE-1; DNA methylation; Hereditary cancer; Gastrointestinal cancer; Lynch syndrome;
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学科分类号
摘要
Increased and decreased methylation at specific sequences (hypermethylation and hypomethylation, respectively) is characteristic of tumor DNA compared to normal DNA and promotes carcinogenesis in multiple ways including genomic instability. Long interspersed element (LINE), an abundant class of retrotransposons, provides a surrogate marker for global hypomethylation. We developed methylation-specific multiplex ligation-dependent probe amplification assays to study LINE-1 methylation in cases of colorectal, gastric, and endometrial cancer (N = 276), stratified by patient category [sporadic; Lynch syndrome (LS); familial colorectal cancer type X (FCCX)] and microsatellite instability status. Within each patient group, LINE-1 showed lower methylation in tumor DNA relative to paired normal DNA and hypomethylation was statistically significant in most cases. Interestingly, normal colorectal mucosa samples from different patient groups displayed differences in LINE-1 methylation that mirrored differences between the respective tumor tissues, with a decreasing trend for LINE-1 methylation from patients with sporadic colorectal cancer to LS to FCCX. Despite the fact that the degree of LINE-1 methylation is generally tissue specific, normal colorectal mucosa, gastric mucosa, and endometrium from LS patients showed similar levels of LINE-1 methylation. Our results suggest that the degree of LINE-1 methylation may constitute a “field defect” that may predispose normal tissues for cancer development.
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页码:827 / 835
页数:8
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[1]  
Ehrlich M(1982)Amount and distribution of 5-methylcytosine in human DNA from different types of tissues of cells Nucleic Acids Res 10 2709-2721
[2]  
Gama-Sosa MA(2009)The impact of retrotransposons on human genome evolution Nat Rev Genet 10 691-703
[3]  
Huang LH(2006)Large-scale structure of genomic methylation patterns Genome Research 16 157-163
[4]  
Midgett RM(2008)CpG island density and its correlations with genomic features in mammalian genomes Genome Biology 9 R79-531
[5]  
Kuo KC(2007)CpG islands: their potential as biomarkers for cancer Expert Rev Mol Diagn 7 519-1985
[6]  
McCune RA(2001)Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes Mol Cell Biol 21 1973-1170
[7]  
Gehrke C(2010)LINE-1 retrotransposition activity in human genomes Cell 141 1159-427
[8]  
Cordaux R(2005)A systematic analysis of LINE-1 endonuclease-dependent retrotranspositional events causing human genetic disease Hum Genet 117 411-408
[9]  
Batzer MA(2008)Activation and transposition of endogenous retroviral elements in hypomethylation induced tumors in mice Oncogene 27 404-508
[10]  
Rollins RA(2009)LINE dancing in the human genome: transposable elements and disease Genome Medicine 1 97-416