期刊
NATURE COMMUNICATIONS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms15099
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资金
- ERA-NET JCT (TRIAGE-MDS)
- HORIZON MDS-RIGHT
- Portuguese Foundation for Science and Technology [SFRH/BD/60391/2009]
- Ministry of Health, Labor and Welfare of Japan
- Japanese Agency for Medical Research and Development
- Japanese Society for the Promotion of Science (JSPS) KAKENHI [26221308, 15H05909, 26890016]
- Grants-in-Aid for Scientific Research [26890016, 15H05912, 26221308, 15H05909] Funding Source: KAKEN
- Fundação para a Ciência e a Tecnologia [SFRH/BD/60391/2009] Funding Source: FCT
Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment. The application of disease-modifying therapy may create an evolutionary bottleneck after which more complex MDS, but also unrelated clones of haematopoietic cells, may emerge. In addition, subclones that acquired an additional mutation associated with treatment resistance (TP53) or disease progression (NRAS, KRAS) may be detected months before clinical changes become apparent. Monitoring the genetic landscape during the disease may help to guide treatment decisions.
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