Genome-wide methylation analysis identifies involvement of TNF-α mediated cancer pathways in prostate cancer - Abstract

Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA. Department of Life Science, Dongguk University-Seoul, Seoul, Republic of Korea.

Altered signaling pathways resulting from aberrant changes in epigenetic parameters may play a pivotal role in carcinogenesis. To identify biological pathways likely to be affected by methylation-mediated alterations in gene expression in prostate cancer, we performed a genome-wide methylation analysis of 27,578 CpG sites, corresponding to 14,495 genes on a pooled sample of 12 pairs of prostate tumor and adjacent normal tissues. In all, 972 CpG sites were significantly hypermethylated while 209 sites were hypomethylated in prostate tumor tissue (FDR adjusted p-value< 0.05; fold change⩾2) corresponding to 1043 unique genes, which is consistent with genome-wide gene-specific hypermethylation patterns previously observed in multiple cancer models. Global hypomethylation in prostate tumor was also detected by measuring methylation changes in ALU repeat sequences. Pathway analysis of the genes with altered methylation patterns identifies the involvement of a cancer related network of genes whose activity may be heavily regulated by TNF-α in prostate tumorigenesis. Our results suggest that epigenetic dysregulation of cellular processes relevant to TNF-α-dependent apoptosis and electrophile detoxification may be intimately involved in prostate carcinogenesis. These findings may lend credence to the possibility of using tumor-specific alterations in methylation patterns as biomarkers in estimating prognosis and assessing treatment options for prostate cancer.

Written by:
Kim SJ, Kelly WK, Fu A, Haines K, Hoffman A, Zheng T, Zhu Y.   Are you the author?

Reference: Cancer Lett. 2011 Mar 1;302(1):47-53.
doi: 10.1016/j.canlet.2010.12.010

PubMed Abstract
PMID: 21237555

UroToday.com Prostate Cancer Section

E-Newsletters

Newsletter subscription

Free Daily and Weekly newsletters offered by content of interest

The fields of GU Oncology and Urology are rapidly advancing. Sign up today for articles, videos, conference highlights and abstracts from peer-review publications by disease and condition delivered to your inbox and read on the go.

Subscribe