LINE-1 hypomethylation in familial and sporadic cancer.

J Mol Med (Berl) 2012 Jul 8;90(7):827-35. Epub 2012 Jan 8.

Department of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, PO Box 63 00014, Finland.

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.

Download full-text PDF

Source
http://link.springer.com/10.1007/s00109-011-0854-z
Publisher Site
http://dx.doi.org/10.1007/s00109-011-0854-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383956PMC
July 2012
13 Reads

Publication Analysis

Top Keywords

line-1 methylation
24
colorectal cancer
8
line-1
8
tumor dna
8
normal colorectal
8
colorectal mucosa
8
methylation
8
normal dna
8
degree line-1
8
normal
5
colorectal
5
cancer
5
dna relative
4
relative paired
4
methylation tumor
4
lower methylation
4
line-1 lower
4
paired normal
4
colorectal gastric
4
dna hypomethylation
4

References

(Supplied by CrossRef)

M Ehrlich et al.
Nucleic Acids Res 1982

R Cordaux et al.
Nat Rev Genet 2009

RA Rollins et al.
Genome Research 2006

L Han et al.
Genome Biology 2008

H Shi et al.
Expert Rev Mol Diagn 2007

M Speek et al.
Mol Cell Biol 2001

CR Beck et al.
Cell 2010

JM Chen et al.
Hum Genet 2005

G Howard et al.
Oncogene 2008

VP Belancio et al.
Genome Medicine 2009

AE Ibrahim et al.
Gut 2011

Similar Publications