Project overview

Breast cancer is the most common class of cancer diagnosed in women worldwide with more than one million cases diagnosed annually (Parkin et al., 2005). Breast cancer is responsible for >400,000 deaths per year (Parkin et al. 2005) making it the leading cause of cancer deaths in women. The aetiology of most breast cancer cases is unknown. However, endocrine factors, genetic susceptibility to the disease and mutagenic exposures such as X-irradiation are all known to influence risk of the disease.

Extraordinary recent advances in sequencing now make it a realistic aim to sequence large numbers of breast cancer genomes to find somatic mutations on a massive scale. We propose to generate comprehensive catalogues of somatic mutations in 500 ER+, HER2-breast cancers under the ICGC model by high coverage, shotgun genome sequencing of both tumour and normal DNA. All classes of mutations are expected to be detected including base substitutions, insertions, deletions, copy number changes, translocations and other chromosomal rearrangements. These catalogues of mutations will afford us statistical power to identify cancer genes that are mutated at a frequency of greater than 3% in this class of breast cancer. They will also carry signatures of past mutagenic processes operative in the development of each cancer and thus provide insights into the aetiology of the disease.

Complementary catalogues of epigenomic changes (genome-wide DNA methylation) will be generated for the same 500 cancer samples together with mRNA and miRNA expression profiles. Integrated analyses of these data will be carried out and compared to parallel datasets from other classes of breast cancer as well as other types of cancer.

The results of this exhaustive and comprehensive set of studies will have enormous impact on our understanding of the causes and biology of breast cancer and will lead to major advances in detection, prevention and treatment in one of the most common diseases and causes of death in the developed world.

As part of the International Cancer Genome Consortium, the Wellcome Trust Sanger Institute (WTSI) has initiated and leads the multi-national ICGC Working Group focused on breast cancer. For more information on these other projects, please click on the links below:

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