期刊
ONCOTARGET
卷 6, 期 8, 页码 5634-5649出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3111
关键词
Breast cancer; Metastasis models; Copy number aberrations; Linear progression model
资金
- Odense University Hospital Free Research Fund
- Harboefonden
- Aase og Ejnar Danielsen Fond
- Fabrikant Einar Willumsens Mindelegat
- Grosserer M. Brogaard og Hustrus Mindefond
- Kong Christian Den Tiendes Fond
- Dagmar Marshalls Fond
- Axel Muusfeldts Fond
- Kraeftfonden
- Raimond og Dagmar Ringgard-Bohns Fond
- Grete og Sigurd Pedersens Fond
- Syddansk Universitets Forskningsfond
- Poul og Ellen Hertz' Fond
- Fonden til Laegevidenskabens Fremme
- Grosserer A.V. Lykfeldt og Hustrus Legat
- Familien Hede Nielsens Fond
- Lykfeldts Legat
- Dansk Kraeftforskningsfond
- Ulla og Mogens Folmer Andersens Fond
- Ingenior K. A. Rohde og Hustrus Legat
- Krista og Viggo Petersens Fond
- Lundbeckfonden Center of Excellence NanoCAN grant
- DAWN project grant from the SDU Excellence program
- Danish Strategic Research Counsil
- DBCG-TIBCAT
Evolution of the breast cancer genome from pre-invasive stages to asynchronous metastasis is complex and mostly unexplored, but highly demanded as it may provide novel markers for and mechanistic insights in cancer progression. The increasing use of personalized therapy of breast cancer necessitates knowledge of the degree of genomic concordance between different steps of malignant progression as primary tumors often are used as surrogates of systemic disease. Based on exome sequencing we performed copy number profiling and point mutation detection on successive steps of breast cancer progression from one breast cancer patient, including two different regions of Ductal Carcinoma In Situ (DCIS), primary tumor and an asynchronous metastasis. We identify a remarkable landscape of somatic mutations, retained throughout breast cancer progression and with new mutational events emerging at each step. Our data, contrary to the proposed model of early dissemination of metastatic cells and parallel progression of primary tumors and metastases, provide evidence of linear progression of breast cancer with relatively late dissemination from the primary tumor. The genomic discordance between the different stages of tumor evolution in this patient emphasizes the importance of molecular profiling of metastatic tissue directing molecularly targeted therapy at recurrence.
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