Mutational landscape and natural history reconstruction of BCP-ALL monozygotic twins. (A) Circos plot (http://circos.ca/) representing the total number of mutations identified at diagnosis for each twin. Twin A is shown in pink (inner ring). Twin B is shown in blue (outer ring). Chromosome ideograms are indicated inside the graph. Copy-number alterations are represented as lines within the gray rings. Venn diagrams inside the graph show the total number of exclusive (pink, twin A; blue, twin B) and shared (yellow) somatic mutations. Coding mutations are annotated outside the graph according to genomic gene location. Substitution mutant allele frequency is shown in brackets. Genomic chromosomal rearrangements are represented with yellow lines connecting chromosomal breakpoints. (B) Graphical reconstruction of the number of mutations accumulated during tumor history. Approximately one-third of the somatic mutations (shown in yellow), including the translocation responsible for the expression of the TCF3-ZNF384 fusion gene, occurred before birth, when both twins shared the same circulatory system. Coding mutations are indicated. Leukemia in both twins evolved independently after birth, with twin-specific postnatal mutations.