Tags: brest | cancer | gene | changes

Study Unpicks Gene Changes behind Breast Cancer

Thursday, 17 May 2012 12:36 PM

 

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Scientists have mapped the complete genetic codes of 21 breast cancers and created a catalog of the mutations that accumulate in breast cells, raising hopes that the disease may be able to be spotted earlier and treated more effectively in future.

The research, the first of its kind, untangles the genetic history of how cancer evolves, allowing scientists to identify mutational patterns that fuel the growth of breast tumours, and start to work out the processes behind them.

"These findings have implications for our understanding of how breast cancers develop over the decades before diagnosis in adults and might help to find possible targets for improved diagnosis or therapeutic intervention in the future," said Mike Stratton, who led the research team.

Breast cancer kills more than 450,000 women a year worldwide and is the most common cancer among women, accounting for 16 percent of all cases, according to the World Health Organisation (WHO).

A study last year by the Institute for Health Metrics and Evaluation in the United States found that global breast cancer cases have more than doubled in just three decades, from 641,000 cases in 1980 to 1.6 million cases in 2010 - a pace that far exceeds global population growth.

"This is the first time we've been able to delve fully into breast cancer genomes in such a thorough way," said Peter Campbell, head of cancer genetics and genomics at the Wellcome Trust Sanger Institute in Cambridge, where the studies were led.

The work had given scientists "a full panoramic view of the cancer genome" and helped them identify "mutational patterns rather than individual mutations in specific genes", he added.

"We've known for many years now that all cancers are due to abnormalities of DNA...that occur in every single cell of the body over the course of a lifetime," said Stratton.

"But although we've known that, it's remarkable how rudimentary our knowledge is about what the processes are that cause these abnormalities, these mutations in our DNA."

Stratton's team sequenced the genomes of the 21 breast cancers and catalogued all the mutations. They found five major processes that cause one letter of code to be changed to another letter. Genetic code comes in four DNA letters, A,C,G and T.

Stratton said one of the most exciting findings was that one of these processes is characterised by small pockets of massively mutated regions of the genome.

This sudden "storm" of mutations is often seen in breast cancers, he explained in an audio briefing.

While his team don't fully understand the process behind these storms, they think it may be down to components of the cell whose normal function is to edit, or mutate, DNA.

"What we believe...is that sometimes in normal cells...this stops functioning properly and over-functions. It causes too many mutations and the accumulation of those mutations pushes the cell along the line to become cancer."

The team found that these and other mutations accumulate in breast cells over many years, initially slowly, but picking up greater momentum as genetic damage builds up.

By the time the breast cancers are large enough to be diagnosed, they are made up of a number of genetically related families of cells, with one family dominating the cancer, Stratton explained.

Mark Walport, director of the Wellcome Trust which helped fund the work, said the results showed how scientists are starting to see the landscape of mutations in breast cancer "in something approaching its full complexity".

"As this work continues, we can hope to understand how breast cancer develops and thus how it might be treated more effectively," he said in a statement.

© 2014 Thomson/Reuters. All rights reserved.

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