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Epigenetic test sorts fatal from manageable prostate cancer

22 October 2018
Appeared in BioNews 972

Researchers have identified a DNA methylation signature that can identify aggressive prostate cancer, with up to 92 percent accuracy. 

The scientists, led by Professor Norman Maitland at the University of York, hope that the 17 epigenetic patterns found could be used to assess a patient's prostate cancer before deciding on treatment.

'The challenge in prostate cancer is how to look at all of these patterns within a cell, but hone in on the gene activity that suggests cancer, and not only this, what type of cancer – dangerous or manageable?' said Professor Maitland. 

Epigenetic mechanisms use molecular markers that change gene expression – tagging which 'books' should be read from the genomic 'library'. These markers explain, for example, why our 200 very different tissues can develop from a single cell and yet have the same DNA sequence. One of the most important epigenetic markers is methylation.

Human prostate cancers display many DNA methylation changes compared with normal prostate tissue. Most cells in prostate cancer are in the layer lining the ducts of the prostate (luminal cells), rather than the deeper so-called basal cells. These cell types have different methylation signatures. This difference has confused previous studies, when it comes to trying to find an overall methylation signature for prostate cancer. In addition, each person's individual varying methylation patterns causes noise in the data.

Amid this epigenetic variation, the challenge is, as Professor Maitland puts it: 'How do we distinguish the tiger cancer cells from the pussycat cancer cells, when there are millions of patterns of chemical alterations going on, many of which will be perfectly healthy?'

In their new study, published in the British Journal of Cancer, researchers from the UK and Canada carried out genome-wide DNA methylation profiling on separate, purified populations of basal and luminal cells, sourced from more than 500 patient-matched tumour and cancer-free samples. They then used a computer algorithm to eliminate noise, which left the team with 17 epigenetic markers for prostate cancer. 

The team tested their 17 markers against prostate cancer data in The Cancer Genome Atlas dataset. They found that they could not only distinguish cancer from healthy tissue samples, but even tell whether the cancer was confined to one organ or had spread.

As a result, the researchers hope that epigenetic profiling of cancer tissue could help to tailor patient treatments, and avoid radiotherapies and chemotherapies that are unlikely to work. 

'Unnecessary prostate treatment has both physical consequences for patients and their families, but is also a substantial financial burden on the NHS, where each operation will cost around £10,000,' Professor Maitland said. 

'Cancers that are contained in the prostate, however, have the potential to be 'actively monitored' which is not only cheaper, but has far fewer negative side-effects in patients with non-life-threatening cancer.'

SOURCES & REFERENCES
Distinguishing fatal prostate cancer from ‘manageable’ cancer now possible
University of York |  18 October 2018
Methylation Markers Distinguish Aggressive from Manageable Prostate Cancer
Genetic Engineering and Biotechnology News |  18 October 2018
Phenotype-independent DNA methylation changes in prostate cancer
British Journal of Cancer |  15 October 2018
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