Recent advances in genome sequencing technologies have enabled a better understanding of genetic alterations in both cancer and non-neoplastic cells. Breast cancer is commonly accompanied by benign breast lesions (BBLs) in the adjacent parenchyma, and it has long been reported that a subset of such BBLs already have acquired genetic alterations such as 1q gains, 16q losses and PI3K–AKT pathway mutations. However, the exact clonal relationship between the alterations found in BBLs and breast cancer has not been fully elucidated.

To begin to understand this relationship, Nishimura et al. performed multi-regional whole genome sequencing on variable areas within breast tissue from patients with breast cancer using laser capture microdissection. Sequenced areas encompassed normal breast lobules, non-proliferative lesions, proliferative lesions with or without atypia, in situ lesions, and invasive carcinomas. The phylogenetic reconstruction revealed that clones carrying the derivative chromosome der(1;16) were the common precursor clones. Multiple most recent common ancestor (MRCA) clones evolved from der(1;16) clones, often giving rise to independent in situ and invasive carcinomas, thereby contributing to intratumoural heterogeneity.