Abstract

Epigenetic Deregulation in Cancer

Clare Stirzaker, Group Leader, Garvan Institute of Medical Research

A combination of both genetic and epigenetic changes contribute to the initiation and progression of cancer. With the advent of genome-wide epigenetic technologies, detailed characterisation of epigenetic deregulation in cancer is now possible. We have previously shown that epigenetic deregulation occurs not only at single genes but can also encompass large chromosomal domains, by a process we have termed Long Range Epigenetic Silencing (LRES). We demonstrated that LRES is a common phenomenon in cancer and involves regional chromatin remodelling, including gain of histone repressive modifications and loss of histone active modifications. We have now also shown the prevalence of cancer-specific regional gene activation by performing epigenome-wide profiling of normal prostate and cancer cells, together with genome-wide expression and methylation studies in clinical prostate cancer samples. We show regional activation of specific prostate cancer associated genes, including KLK3 encoding PSA. Our results highlight the prevalence of regional activation in prostate cancer and determine the predominant chromatin and DNA methylation changes associated with cancer-specific gene activation covering large genomic domains.