The largest-ever study to sequence the whole genomes of breast cancers has led scientists to declare that they now have the most comprehensive picture ever of how the disease develops.

Researchers uncovered five new genes associated with the disease and 13 new mutational signatures that influence tumour development, as part of work led by Dr Serena Nik-Zainal of the Wellcome Trust Sanger Institute. The team analysed 560 breast cancer genomes, 556 from women and four from men, in an international collaboration including breast cancer patients from around the world, including the USA, Europe and Asia. Each person’s cancer genome is a historical account of the genetic changes that they have acquired throughout life. As a person develops from a fertilised egg into adulthood, the DNA in their cells gather genetic changes along the way.

Dr Nik-Zainal’s team hunted for mutations that encourage cancers to grow and looked for mutational signatures in each patient’s tumour. They found that women who carry the BRCA1 or BRCA2 gene, and so have increased risk of developing breast and ovarian cancer, had whole cancer genome profiles that were highly distinctive from each other and were also very different to other breast cancers. This discovery could be used to classify patients more accurately for treatment. Dr Zainal said:” In the future, we’d like to be able to profile individual cancer genomes so that we can identify the treatment most likely to be successful for a woman or man diagnosed with breast cancer. It is a step closer to personalised healthacre for cancer.”

The work has been funded through the ICGC Breast Cancer Working group by the Breast Cancer Somatic Genetics Study (BASIS), a European research project funded by the European Community. Collaborator Dr Ewan Birney, from the European Bioinformatics Institute, said: “We know genetic changes and their position in the cancer genome influence how a person responds to a cancer therapy. “For years we have been trying to figure out if parts of DNA that don’t code for anything specific have a role in driving cancer development. This study both gave us the first large scale view of the rest of the genome, uncovering some new reasons why breast cancer arises, and gave us an unexpected way to characterize the types of mutations that happen in certain breast cancers.”

Professor Sir Mike Stratton, Director of the Wellcome Trust Sanger Institute, said: “All cancers are due to mutations that occur in all of us in the DNA of our cells during the course of our lifetimes. Finding these mutations is crucial to understanding the causes of cancer and to developing improved therapies.

“This huge study, examining in great detail the many thousands of mutations present in each of the genomes of 560 cases brings us much closer to a complete description of the changes in DNA in breast cancer and thus to a comprehensive understanding of the causes of the disease and the opportunities for new treatments.”