Single-cell whole-genome sequencing reveals convergent evolution in Burkitt lymphoma.

Burkitt lymphoma carries multiple oncogenic drivers yet arises predominantly in children, whose normal cells harbour few age-related mutations. To investigate this paradox, we seek to define the sequence and timing of mutational drivers underlying Burkitt lymphoma development. Here, we analyse single-cell whole-genome sequencing data of 250 paired normal and malignant B-cells from Burkitt lymphoma patients and integrate this data with 21 bulk WGS samples and an existing dataset of 157 clonally expanded B-cells from healthy individuals. Phylogenetic reconstruction reveals an accelerated accumulation of mutations following the emergence of the most recent common ancestor, leading to the early establishment of extensive genetic intratumoural heterogeneity. We further provide evidence that convergent evolution shapes this diversity at both the point mutation- and copy number variation-levels. This in-depth characterisation further establishes Burkitt lymphoma as a paradigmatic model of tumorigenesis with implications for therapeutic intervention.