Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer. Despite impressive improvements in treatment strategies during recent decades, 20% of the patients die from relapsed disease or treatment-related complications. Why patients with similar clinical presentation and identical treatment differ in their response to therapy is poorly understood. A possible explanation is that drugs only target a subset of the leukemic cells because of clonal heterogeneity. Clonal heterogeneity and evolution in ALL samples has been detected by cytogenetic methods and copy number profiling.
In this project, we will sequence the complete genomes of diagnostic, relapse and germline samples from 30 ALL patients, and determine the allele fractions of somatic single nucleotide variants genome-wide by target capture and deep sequencing. This data enable analysis of clonal heterogeneity and evolution of ALL cells in much more detail than previous studies. Our project will provide a detailed map of the evolving genomes of 30 ALL patients, increase the understanding of the biology of ALL and potentially detect previously unknown genetic factor associated with relapse and treatment failure in ALL.