orals International Association for Breast Cancer Research 2014

Methylome sequencing reveals distinct methylation clusters associated with breast cancer (#3)

Susan Clark 1 , Elena Zotenko 2 , Warwick Locke 2 , Andrew Stone 2 , Clare Stirzaker 2
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Epigenetics Program, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia

Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue from triple negative breast cancer (TNBC) and matched normal samples. We identify differentially methylated regions (DMRs) enriched in promoters associated with transcription factors and axon guidance signaling pathway genes. Importantly, we stratify TNBCs into three distinct methylation clusters associated with better or worse prognosis and identify 17 DMRs that show a strong association with overall survival. Our data reveals coordinated hypermethylation can occur in ER-ve disease and that characterising the epigenetic framework provides a potential signature to stratify TNBCs. Together our findings demonstrate the feasibility of profiling the cancer methylome with limited archival tissue to identify regulatory regions associated with cancer.