Subclonal diversification of primary breast cancer

Dataset ID Technology Samples
EGAD00001000898 Illumina HiSeq 2000 42

Dataset Description

Cancers are ecosystems of genetically related clones, competing across space and time for limited resources. To understand the clonal structure of primary breast cancer, we applied genome and targeted sequencing to 295 samples from 49 patients’ tumors. The extent of subclonal diversification varied considerably among patients and encompassed many spatial patterns, including local growth, intraductal dissemination and clonal intermixture. Landmarks of disease progression, such as acquiring invasive or metastatic potential, arose within detectable subclones of antecedent lesions, suggesting that subclonal mutations could be relevant if actionable. No defined temporal order of mutation was evident, with the commonest genes, including PIK3CA, TP53, BRCA2, PTEN and MYC, mutated early in some, late in others, often exhibiting parallel evolution across subclones. Signatures of homologous recombination deficiency correlated with response to neoadjuvant chemotherapy. Thus, the interplay of mutation, growth and competition drives clonal structures of breast cancer that are complex, variable across patients and clinically relevant.

Data Use Conditions


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Label Code Version Modifier
obsolete general research use and clinical care DUO:0000005 2017-10-16
obsolete research use only DUO:0000014 2017-10-16
publication required DUO:0000019 2017-10-16
user specific restriction DUO:0000026 2017-10-16
institution specific restriction DUO:0000028 2017-10-16