| Autor: |
Karen Page, Daniel Fernandez-Garcia, David S. Guttery, Cathy J. Richards, A.B. Moreno-Cardenas, L Primrose, Mark R Openshaw, Sharif Uddin Ahmed, Bradley J. Toghill, Luke Martinson, Josep Tabernero, R.A. Toledo, M. Vazquez, Robert K. Hastings, R. C. Coombes, Anne Thomas, Jacqui Shaw, K Kulbicki |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.1101/2020.01.10.901330 |
| Popis: |
Little is known about the metastatic evolutionary dynamics of BRCA2-mutated cancers. Here, we applied whole-exome sequencing (WES) of primary tumor (PT), local relapse (LR) and eight serial plasma cfDNA samples collected from disease progression to depict the 12 years evolutionary trajectory of a metastatic BRCA2-mutated breast cancer. While longitudinal WES-cfDNA recapitulated clonal and subclonal mutations and copy number profiles detected in LR, emergence of plasma-exclusive mutations in TSC2 and HDAC9 cancer-related genes and loss of HLA loci as an immune escape mechanism were also detected. Lastly, mutation signature 3, associated with homologous recombination deficiency and response to platinum-based therapy raised profoundly from 19% in PT to 60% in late stage disease. In conclusion, we show for the first time that longitudinal WES-cfDNA enables the evolutionary trajectory of advanced cancer to be uncovered and that increment of MS3 and loss of HLA are key players in this BRCA2-mutated breast metastasis. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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