| Literature DB >> 31570896 |
Lindsay Angus1, Marcel Smid1, Saskia M Wilting1, Job van Riet1,2,3, Arne Van Hoeck4, Luan Nguyen4, Serena Nik-Zainal5, Tessa G Steenbruggen6, Vivianne C G Tjan-Heijnen7, Mariette Labots8, Johanna M G H van Riel9, Haiko J Bloemendal10,11, Neeltje Steeghs6,11, Martijn P Lolkema1,11, Emile E Voest6,11, Harmen J G van de Werken2,3, Agnes Jager1, Edwin Cuppen4,12, Stefan Sleijfer1,11, John W M Martens13,14.
Abstract
The whole-genome sequencing of prospectively collected tissue biopsies from 442 patients with metastatic breast cancer reveals that, compared to primary breast cancer, tumor mutational burden doubles, the relative contributions of mutational signatures 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 patients pretreated with fluorouracil, taxanes, platinum and/or eribulin, whereas the de novo mutational signature I identified in this study is significantly associated with pretreatment containing platinum-based chemotherapy. Clinically relevant subgroups of tumors are identified, exhibiting either homologous recombination deficiency (13%), high tumor mutational burden (11%) or specific 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.Entities:
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Year: 2019 PMID： 31570896 PMCID： PMC6858873 DOI： 10.1038/s41588-019-0507-7
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330