In primary untreated breast cancers, multi-region sequencing has highlighted that the extent of subclonal diversification varies considerably among individual tumours with no strict temporal order being evident, and genomic alterations such as point mutations and rearrangements affect the most common breast cancer genes, including PIK3CA, TP53, PTEN, BRCA2 and MYC, occurring early in some tumours and late in others21. This evidence concerns the gene TP53 and breast carcinoma.