Epigenetic regulation of human epithelial cell cancers.
Cancer is the second leading cause of death in industrialized countries, with epithelial cell cancers (carcinomas) representing approximately 85% of all diagnosed cancers. The 5-year survival rate for many carcinomas remains low, highlighting the requirement for improved diagnosis and more effective therapies. Epigenetic modifications that do not involve changes in the DNA sequence, but result in changes in gene expression, are rapidly being realized as important in carcinogenesis. Evidence is emerging that DNA methylation, histone modification and alternative mRNA splicing are involved in various human epithelial cell cancers, and diagnostic and therapeutic strategies based on these epigenetic phenomena are under investigation. This review provides an overview of studies demonstrating the importance of epigenetic regulation of gene expression in the diagnosis, progression and response to treatment of human carcinomas. The use of therapeutic agents to reverse these epigenetic changes, either as single treatments or in combination with other therapies, is also discussed.
Shelton
Bradley P
BP
Lung Institute of Western Australia, Centre for Asthma, Allergy and Respiratory Research, The University of Western Australia, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, WA 6009, Australia.
Misso
Neil L
NL
Shaw
Odette M
OM
Arthaningtyas
Estri
E
Bhoola
Kanti D
KD
D017398:Alternative Splicing; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D019175:DNA Methylation; D004260:DNA Repair; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans
D006657:Histones