BioProject

Most types of cancers are made up of heterogeneous mixtures of genetically distinct subclones. More...

Most types of cancers are made up of heterogeneous mixtures of genetically distinct subclones. In particular, acute myeloid leukemia (AML) has been shown to undergo substantial clonal evolution over the course of the disease. AML tends to harbor fewer mutations than solid tumours, making it challenging to infer clonal structure. Here, we present a nine-year, whole-exome sequencing study of a single case at twelve time points, from the initial diagnosis until a 4th relapse, including six remission samples in-between. To the best of our knowledge, it covers the longest timespan of any dataset of its kind. We used this time series data to track the hierarchy and order of variant acquisition, and subsequently analyzed the evolution of somatic variants to infer clonal structure. From this, we postulate the development and extinction of subclones, as well as their anti-correlated expansion via varying drug responses. In particular, we show that new subclones started appearing after the 1st complete remission (CR). The presence and absence of different subclones during remission and relapses implies differing drug responses among subclones. Our study shows that time series analysis contrasting remission and relapse periods provides a much more comprehensive view of clonal structure and evolution. Less...