All cancers carry somatic mutations in their genomes. A subset, known as driver mutations, confer clonal selective advantage on cancer cells and are causally implicated in oncogenesis, and the remainder are passenger mutations. The driver mutations and mutational processes operative in breast cancer have not yet been comprehensively explored. Here we examine the genomes of 100 tumours for somatic copy number changes and mutations in the coding exons of protein-coding genes. The number of somatic mutations varied markedly between individual tumours. We found strong correlations between mutation number, age at which cancer was diagnosed and cancer histological grade, and observed multiple mutational signatures, including one present in about ten per cent of tumours characterized by numerous mutations of cytosine at TpC dinucleotides. Driver mutations were identified in several new cancer genes including AKT2, ARID1B, CASP8, CDKN1B, MAP3K1, MAP3K13, NCOR1, SMARCD1 and TBX3. Among the 100 tumours, we found driver mutations in at least 40 cancer genes and 73 different combinations of mutated cancer genes. The results highlight the substantial genetic diversity underlying this common disease.

Original publication

DOI

10.1038/nature11017

Type

Journal article

Journal

Nature

Publication Date

16/05/2012

Volume

486

Pages

400 - 404

Keywords

Age Factors, Breast Neoplasms, Cell Transformation, Neoplastic, Cytosine, DNA Mutational Analysis, Female, Humans, JNK Mitogen-Activated Protein Kinases, Mutagenesis, Mutation, Neoplasm Grading, Oncogenes, Reproducibility of Results, Signal Transduction