New epigenetic study offers potential for further stratification in triple negative breast cancer.

A study led by the Epigenetics Group in the Cancer Division of the Garvan Institute of Medical Research in Australia, was published this month in Nature Communications. The group investigated differences in the methylation of triple-negative breast cancers that might help develop diagnostic tests.

When a tumour does not over-express or amplify HER2 and lack estrogen and progesterone receptors, it is said to be ‘Triple Negative’. With varying rates of progression, this cancer can be very difficult to manage. Patient stratification and the development of companion diagnostics offer the potential for increasingly efficient treatment.

The full study can be read via Nature Communications

Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value

Clare Stirzaker, Elena Zotenko, et al.


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 with promoters associated with transcription factor binding sites and DNA hypersensitive sites. 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, including DMRs located in the ​Wilms tumour 1 (​WT1) gene, bi-directional-promoter and antisense ​WT1-AS. Our data reveal that coordinated hypermethylation can occur in ​oestrogen receptor-negative disease, and that characterizing 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.

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