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As oncologists acquire the technology to read the DNA of individual cells, they are learning about the remarkable genetic diversity of cancer in each patient. The latest study of breast cancer at the University of Texas shows that no two tumour cells in a single patient have an identical genome. The researchers say their findings, published in Nature, have important implications for the diagnosis and treatment of breast cancer.

The team used a new DNA sequencing approach called Nuc-seq to study mutations in thousands of cells in individual patients. They discovered a huge range of genetic changes taking place, at a rate that differed between types of cancer: in hormone-sensitive “oestrogen receptor positive” breast cancer the mutation rate remained constant as the cancer developed, while in “triple negative” tumours (which are not responsive to hormone treatment) the mutation rate rose.

An important question about chemotherapy is whether resistant mutations already exist in a few rare cells in the tumour before treatment begins or whether they arise through natural selection as the cancer evolves during therapy.

“While this question has been studied for decades in bacteria, it remains poorly understood in most human cancers,” says Nicholas Navin, the study leader. “Our data suggest that a large number of diverse mutations are likely to be pre-existing in the tumour prior to chemotherapy. Therefore we expect that measuring genomic diversity may also have prognostic value in identifying which patients will develop resistance to chemotherapy.”

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