Epigenetic signatures that differentiate triple-negative breast cancers

04-Feb-2015 - Australia

A new study, published in Nature Communications, compares the breast cancer DNA 'methylome' with that of healthy individuals. The methylome provides a new picture of the genome and shows how it is epigenetically 'decorated' with methyl groups, a process known as DNA 'methylation'. The study reveals "distinct methylation patterns" in the primary biopsy breast cancer cells indicating better or worse prognosis.

Dr Kate Patterson

The methylating enzyme DNMT (purple) cradles the DNA molecule as a methyl group is added to DNA.

Triple-negative breast cancers, which make up 15-20% of all breast cancers, lack any of the three receptors (oestrogen, progesterone or HER2) that would make them responsive to targeted drugs. Overall, patients have a higher risk of disease recurrence and shorter survival than those with other breast cancers. Triple-negative breast cancer patients tend to fall into two categories: those that succumb to their disease within 3-5 years, regardless of treatment; and those that remain disease free for longer than the average non-triple-negative breast cancer patient (at least 8 years post-diagnosis).

At present, there is no reliable way to 'stratify' triple-negative cancers into these two sub-groups. Clinicians use tumour size, degree of spread, and infiltration of lymph nodes to determine whether a patient falls into a high-risk or low-risk category. Ironically, the outcome of triple-negative breast cancers is far less associated with cancer stage than other breast cancers.

Professor Susan Clark, Dr Clare Stirzaker and Dr Elena Zotenko from Sydney's Garvan Institute of Medical Research, performed whole genome methylation capture sequencing on archival tissue samples from triple negative breast cancer patients and matched normal samples, followed by next generation sequencing to determine cancer-specific changes in DNA methylation.

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