The most comprehensive analysis to date of somatic (acquired) mutations, across whole-genome sequences for breast cancer, is reported in a paper published this week in Nature. A related paper, published in Nature Communications, explores how these mutations relate to aspects of genome structure. Together, the studies highlight the repertoire of genes and mutational processes involved in breast cancer and move us closer to a more complete account of the genetic basis of the disease.
Most currently available breast cancer sequences relate only to the parts of the genome that code for proteins (exome sequences, covering protein-coding regions), leaving many of the central questions about the molecular pathogenesis of the disease unresolved.
Serena Nik-Zainal, Michael Stratton and colleagues sequenced the whole genome of tumours and normal tissue from 560 breast cancer patients (556 female, 4 male), across both protein-coding regions and, representing an important advance, also non-coding regions. They identify mutations in 93 genes that are implicated in the genesis of disease. The authors identified several mutational signatures in these cancer genomes that are associated with defective DNA repair and the function of the tumour suppressor genes BRCA1 or BRCA2.
In the second paper, Serena Nik-Zainal and colleagues use the same 560 breast cancer genomes to show that specific mutational signatures are associated with elements of genomic architecture, and the timing of when parts of the genome are replicated.