LINE-1 methylation in the peripheral blood mononuclear cells of cancer patients.
BACKGROUND
Recently, we classified LINE-1 loci according to their methylation statuses and found that the percentage of hypomethylated LINE-1 loci ((u)C(u)C) can differentiate between the peripheral blood mononuclear cells (PBMCs) of oral cancer patients and normal controls with a higher specificity and sensitivity than overall methylation levels. Here, we evaluated the LINE-1 methylation levels and patterns in PBMCs from patients with cancers of the nasopharynx, lung, liver, bile duct, breast and colon.


METHODS
Combined Bisulfite Restriction Analysis (COBRA) of LINE-1 loci was performed to examine the LINE-1 methylation statuses of PBMCs from 216 cancer patients with 6 different types of cancer compared with 144 normal controls.


RESULTS
Only colorectal and nasopharyngeal cancer samples were found to have lower levels of overall LINE-1 methylation compared with normal controls (p<0.0001 and p=0.0022). However, %(u)C(u)C in cancers of the colon, liver, lung and nasopharynx was significantly higher compared with normal controls (p<0.0001, p<0.0001, p=0.01 and p=0.001, respectively). Furthermore, ROC curve analyses of these four cancer types also demonstrated the potential of %(u)C(u)C as a biomarker for cancer diagnosis.


CONCLUSIONS
Changes in the levels and patterns of genome-wide methylation of PBMCs are associated with cancer risk. For LINE-1, %(u)C(u)C is a more effective tumour marker for determining cancer risk than overall methylation levels.
Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University, Bangkok 10400, Thailand.
Nakarin
N
Kitkumthorn
Time
T
Tuangsintanakul
Prakasit
P
Rattanatanyong
Danai
D
Tiwawech
Apiwat
A
Mutirangura
D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor