Researchers at the Wellcome Trust Sanger Institute have begun to unravel the complex processes that cause breast cancer, identifying a variety of genetic mutations that emerge during tumor growth.
Their research found that a variety of naturally-occurring mutations in the DNA cells can initiate different sequences of mutations that eventually lead to breast cancer.
“What emerges is a really complex landscape of mutation, where each cancer seems to have been generated by a different combination of mutation processes,” said Professor Mike Stratton, author and Director of the Wellcome Trust Sanger Institute.
The researchers cataloged of all the mutations in the genomes of 21 breast cancers, discovering almost 200,000 different mutations. The different mutations were associated with different periods in the development of a breast tumor, revealing previously unknown patterns of mutation.
“We are used to thinking about Darwinian evolution of species by natural selection taking place over centuries and millennia. But in cancer and infectious disease similar processes can be observed over much shorter periods,” said Sir Mark Walport, Director of the Wellcome Trust. “These studies, which follow from the human genome project, are untangling the evolutionary processes that eventually lead to breast cancer, in a way that would have been impossible only a few years ago.
“We are starting to see the landscape of mutation that characterizes this disease in something approaching its full complexity for the first time. As this work continues, we can hope to understand how breast cancer develops and thus how it might be treated more effectively.”
Their research was published online on 17 May in Cell.
Mutations slowly accumulate in breast cells over many years, but the researchers found that in 13 of the 21 breast cancer genomes they evaluated there were sporadic bursts of mutations. The researchers named this newly discovered phenomenon kataegis, from the Greek word for thunderstorm.
“In kataegis, a large number of mutations occur very close together in the genome,” says Dr Serena Nik-Zainal, first author from the Wellcome Trust Sanger Institute. “They show a distinguishing mutational motif and frequently co-occur with large-scale rearrangements: it is a unique mutational pattern.”
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