Characterization of age signatures of DNA methylation in normal and cancer tissues from multiple studies

BMC Genomics

KiYoung Lee²  Gyesoon Yoon¹  Hyosil Kim²  Kyung Kim²  Jihyun Kim² 

[1]Department of Biochemistry, Ajou University School of Medicine, Suwon 443-721, South Korea

[2]Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon 443-380, South Korea

关键词: Cancer;    Systems biology;    Meta-analysis;    Aging;    Age signature;    Epigenetics;    DNA methylation;   

Others  :  1092147
DOI  :  10.1186/1471-2164-15-997

 received in 2014-03-07, accepted in 2014-08-18,  发布年份 2014

【 摘 要 】

Background

DNA methylation (DNAm) levels can be used to predict the chronological age of tissues; however, the characteristics of DNAm age signatures in normal and cancer tissues are not well studied using multiple studies.

Results

We studied approximately 4000 normal and cancer samples with multiple tissue types from diverse studies, and using linear and nonlinear regression models identified reliable tissue type-invariant DNAm age signatures. A normal signature comprising 127 CpG loci was highly enriched on the X chromosome. Age-hypermethylated loci were enriched for guanine–and-cytosine-rich regions in CpG islands (CGIs), whereas age-hypomethylated loci were enriched for adenine–and-thymine-rich regions in non-CGIs. However, the cancer signature comprised only 26 age-hypomethylated loci, none on the X chromosome, and with no overlap with the normal signature. Genes related to the normal signature were enriched for aging-related gene ontology terms including metabolic processes, immune system processes, and cell proliferation. The related gene products of the normal signature had more than the average number of interacting partners in a protein interaction network and had a tendency not to interact directly with each other. The genomic sequences of the normal signature were well conserved and the age-associated DNAm levels could satisfactorily predict the chronological ages of tissues regardless of tissue type. Interestingly, the age-associated DNAm increases or decreases of the normal signature were aberrantly accelerated in cancer samples.

Conclusion

These tissue type-invariant DNAm age signatures in normal and cancer can be used to address important questions in developmental biology and cancer research.

【 授权许可】

   
2014 Kim et al.; licensee BioMed Central Ltd.

【 图 表 】

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