» Articles » PMID: 26338779

Epigenetic Instability of Imprinted Genes in Human Cancers

Overview
Specialty Biochemistry
Date 2015 Sep 5
PMID 26338779
Citations 38
Authors
Affiliations
Soon will be listed here.
Abstract

Many imprinted genes are often epigenetically affected in human cancers due to their functional linkage to insulin and insulin-like growth factor signaling pathways. Thus, the current study systematically characterized the epigenetic instability of imprinted genes in multiple human cancers. First, the survey results from TCGA (The Cancer Genome Atlas) revealed that the expression levels of the majority of imprinted genes are downregulated in primary tumors compared to normal cells. These changes are also accompanied by DNA methylation level changes in several imprinted domains, such as the PEG3, MEST and GNAS domains. Second, these DNA methylation level changes were further confirmed manually using several sets of cancer DNA. According to the results, the Imprinting Control Regions of the PEG3, MEST and GNAS domains are indeed affected in breast, lung and ovarian cancers. This DNA methylation survey also revealed that evolutionarily conserved cis-regulatory elements within these imprinted domains are very variable in both normal and cancer cells. Overall, this study highlights the epigenetic instability of imprinted domains in human cancers and further suggests its potential use as cancer biomarkers.

Citing Articles

Methylome profile of medaka eggs and sperm.

Wang X, Bhandari R Epigenetics. 2024; 19(1):2417151.

PMID: 39428969 PMC: 11497970. DOI: 10.1080/15592294.2024.2417151.


Novel epigenetic molecular therapies for imprinting disorders.

Wang S, Jiang Y Mol Psychiatry. 2023; 28(8):3182-3193.

PMID: 37626134 PMC: 10618104. DOI: 10.1038/s41380-023-02208-7.


Epigenetic reprogramming in cancer: From diagnosis to treatment.

Costa P, Sales S, Pinheiro D, Pontes L, Maranhao S, Pessoa C Front Cell Dev Biol. 2023; 11:1116805.

PMID: 36866275 PMC: 9974167. DOI: 10.3389/fcell.2023.1116805.


MC profiling: a novel approach to analyze DNA methylation heterogeneity in genome-wide bisulfite sequencing data.

De Riso G, Sarnataro A, Scala G, Cuomo M, Della Monica R, Amente S NAR Genom Bioinform. 2023; 4(4):lqac096.

PMID: 36601577 PMC: 9803872. DOI: 10.1093/nargab/lqac096.


Increased copy number of imprinted genes in the chromosomal region 20q11-q13.32 is associated with resistance to antitumor agents in cancer cell lines.

Krushkal J, Vural S, Jensen T, Wright G, Zhao Y Clin Epigenetics. 2022; 14(1):161.

PMID: 36461044 PMC: 9716673. DOI: 10.1186/s13148-022-01368-7.


References
1.
Barlow D, Bartolomei M . Genomic imprinting in mammals. Cold Spring Harb Perspect Biol. 2014; 6(2). PMC: 3941233. DOI: 10.1101/cshperspect.a018382. View

2.
Lutsik P, Feuerbach L, Arand J, Lengauer T, Walter J, Bock C . BiQ Analyzer HT: locus-specific analysis of DNA methylation by high-throughput bisulfite sequencing. Nucleic Acids Res. 2011; 39(Web Server issue):W551-6. PMC: 3125748. DOI: 10.1093/nar/gkr312. View

3.
Shen Y, Yue F, McCleary D, Ye Z, Edsall L, Kuan S . A map of the cis-regulatory sequences in the mouse genome. Nature. 2012; 488(7409):116-20. PMC: 4041622. DOI: 10.1038/nature11243. View

4.
Lim D, Maher E . Genomic imprinting syndromes and cancer. Adv Genet. 2010; 70:145-75. DOI: 10.1016/B978-0-12-380866-0.60006-X. View

5.
Witte T, Plass C, Gerhauser C . Pan-cancer patterns of DNA methylation. Genome Med. 2014; 6(8):66. PMC: 4254427. DOI: 10.1186/s13073-014-0066-6. View