Epigenetic signature helps to diagnose rare breast tumour

The epigenetic signature of a rare, hard-to-diagnose breast tumour has been found by a team led by the Garvan Institute of Medical Research. Their discovery, published in The Journal of Pathology, could lead to improved treatment guidelines and better outcomes for patients with this rare disease.

Accounting for less than 1% of breast tumours, phyllodes tumours can be difficult to diagnose due to their similarity under the microscope to other types of breast tumours. Most phyllodes tumours are benign, but 10% are malignant. Accurate diagnosis is crucial for effective treatment, as misdiagnosis results in inappropriate or delayed treatment.

“The current way of diagnosing phyllodes tumours is to analyse their cellular features under a microscope, but this technique means they can be misdiagnosed as cellular fibroadenomas, sarcomas or metaplastic breast cancer — tumour types that may look the same but have very different growth rates, prognoses and treatment pathways,” said co-senior author Dr Ruth Pidsley, Leader of the DNA Methylation Biomarkers Group at Garvan.

Researchers have now found that new epigenetic-based DNA markers may give additional information for diagnosis. Epigenetic changes affect whether gene activity is turned up or down without altering the DNA sequence, and can be influenced by environmental factors.

A common epigenetic mechanism is DNA methylation, where molecules called methyl groups attach to parts of DNA, which can change gene expression. Analysing samples from 33 patients, the researchers found that phyllodes tumours exhibit a unique DNA methylation pattern, allowing them to be distinguished from other cancers.

“In addition to finding this new epigenetic signature, we identified an additional methylation pattern that could be used to differentiate malignant phyllodes tumours from benign cases,” said Dr Braydon Meyer, Research Officer in Garvan’s Cancer Epigenetics Lab. “We also developed an algorithm that reclassified originally misdiagnosed samples.”

“Altered DNA methylation patterns have been instrumental in diagnosing other cancer types, showing the broader potential of epigenetic biomarkers in precision cancer diagnosis and personalised treatment,” added Associate Professor Clare Stirzaker, Leader of Garvan’s Cancer Epigenetic Biomarker Group and co-first author on the paper. The new understanding could lead to improved diagnosis, treatment and outcomes.

“Disruption to epigenetic processes, such as DNA methylation patterns, is a recognised hallmark of cancer and can vary significantly between cancer types, allowing a unique cancer forensic signature,” said co-senior author Professor Susan Clark, Head of the Cancer Epigenetics Lab.

“Harnessing the power of cutting-edge epigenetic technologies, like digital droplet PCR, our next step will be devising a sensitive epigenetic-based PCR test to detect phyllodes tumours that could be routinely used in pathology laboratories.”

Image caption: A phyllodes tumour’s characteristic leaf-like cellular structure is not enough to identify it as malignant or benign, as in this borderline case.