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| Home > External Publications > Vita Publications > The genomic landscape of metastatic breast cancer highlights changes in mutation and signature frequencies |
| Journal Article | DKFZ-2022-01682 |
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2019
Macmillan Publishers Limited, part of Springer Nature
London
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Please use a persistent id in citations: doi:10.1038/s41588-019-0507-7
Abstract: The whole-genome sequencing of prospectively collected tissue biopsies from 442 patients with metastatic breast cancerreveals that, compared to primary breast cancer, tumor mutational burden doubles, the relative contributions of mutationalsignatures shift and the mutation frequency of six known driver genes increases in metastatic breast cancer. Significant associations with pretreatment are also observed. The contribution of mutational signature 17 is significantly enriched in patientspretreated with fluorouracil, taxanes, platinum and/or eribulin, whereas the de novo mutational signature I identified in thisstudy is significantly associated with pretreatment containing platinum-based chemotherapy. Clinically relevant subgroups oftumors are identified, exhibiting either homologous recombination deficiency (13%), high tumor mutational burden (11%) orspecific alterations (24%) linked to sensitivity to FDA-approved drugs. This study provides insights into the biology of metastatic breast cancer and identifies clinically useful genomic features for the future improvement of patient management.
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