MELBOURNE: Decoding the letters of the human genome revolutionised scientists understanding of the role of genetic mutations in many diseases, including about one in every five cancers.
Now a team of Australian scientists have gone a step further, inventing a way to decipher another layer of information that garnishes genes, called methyl groups, which may explain the cause of many more cancers, The Age reported. Methyl groups hang off sections of DNA like Christmas lights and act like a switch, affecting how genes are expressed in different cell types.
Collectively called the methylome, they can also switch off tumour suppressor genes and switch on cancer promoting genes. Professor Susan Clark from the Garvan Institute of Medical Research and her team have for first the first time translated the methylome of breast cancer, finding distinct patterns associated with different types of breast cancer.
They have also found a way to classify women with the worst type of breast cancer, triple-negative, into two groups; those with a highly aggressive form and those with a lower-risk variety with a longer survival time. At present there is no reliable way to divide triple-negative cancers, which do not respond to targeted treatment, into these sub-groups. With further testing, methylation signatures may be used as predictive biomarkers that doctors use to prescribe more appropriate treatments for women diagnosed with breast cancer in the future.
Clarks team are the first in the world to sequence large chunks of the methylome from samples of cancer tissue that had been archived for up to two decades. Using historical samples meant they could trace which methylation patterns were linked to patient survival times. Cancer specialist Dr Paul Mainwaring, who was not involved in the research, said Clarks new technique to decode the entire methylome will have significant implications for cancer research in general.
The power of this technology is that its allowing us to get a much sharper view on how cancer starts, progresses, metastasises, behaves and a new avenue of treatment, said Dr Mainwaring from Icon Cancer Care in Brisbane. Well still be talking about this paper in 20 years, he said.
While specific faults in a persons DNA sequence have been shown to increase their risk of certain cancers the BRCA 2 mutation which significantly increases a womans chance of developing breast tumours in about two-thirds of cancers there are no changes to the DNA code.
In many of these cases scientists are finding changes to the genome that do not affect the underlying code, principally through DNA methylation. Every cancer has some sort of mutational profile, but there are multiple layers of where those abnormalities can occur. This is a giving us the ability to read one of those layers, he said.
Dr Mainwaring said the exciting part about identifying methylation patterns was that they are potentially reversible. Its the bit of the genome we may be able to influence most, certain regions can be changed either by diet, exercise or drugs, he said. Clark and teams research was funded by the National Breast Cancer Foundation and has been published in the leading scientific journal Nature Communications.
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