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.

• MeSH
• Bone Marrow Cells drug effects   metabolism   pathology   MeSH
• Drug Resistance, Neoplasm genetics   MeSH
• GTP Phosphohydrolases genetics   metabolism   MeSH
• Angiogenesis Inhibitors therapeutic use   MeSH
• Clonal Evolution drug effects   MeSH
• Lenalidomide MeSH
• Middle Aged MeSH
• Humans MeSH
• Disease Management MeSH
• Membrane Proteins genetics   metabolism   MeSH
• Monitoring, Physiologic MeSH
• Mutation MeSH
• Myelodysplastic Syndromes drug therapy   genetics   metabolism   pathology   MeSH
• Biomarkers, Tumor genetics   metabolism   MeSH
• Tumor Suppressor Protein p53 genetics   metabolism   MeSH
• Follow-Up Studies MeSH
• Disease Progression MeSH
• Proto-Oncogene Proteins p21(ras) genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• Exome Sequencing MeSH
• Aged MeSH
• Thalidomide analogs & derivatives   therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• GTP Phosphohydrolases MeSH
• Angiogenesis Inhibitors MeSH
• KRAS protein, human MeSH Browser
• Lenalidomide MeSH
• Membrane Proteins MeSH
• Biomarkers, Tumor MeSH
• Tumor Suppressor Protein p53 MeSH
• NRAS protein, human MeSH Browser
• Proto-Oncogene Proteins p21(ras) MeSH
• Thalidomide MeSH
• TP53 protein, human MeSH Browser