Figure 4. Hematopoietic Clones and Evolution in Three Patients Who Subsequently Received a Diagnosis of Myeloid Cancer.

Panels A and B show the allelic fraction and coverage for rare heterozygous variants ascertained through whole-genome sequencing in Participant 1 and Participant 2, respectively, each of whom received a diagnosis of myeloid cancer 2 months after DNA sampling. Blue shading indicates the strength of evidence that a mutation was somatically acquired, with the negative log₁₀ P value for the mutation being at an allelic fraction of less than 50% according to a binomial test. Mutations in black were initially ascertained through whole-exome sequencing. Mutations in red are candidate driver mutations. The histograms show the overall distribution of allelic fractions, with the candidate driver mutations indicated in red. Panel C shows the progression from clonal hematopoiesis to myeloid cancer in Participant 3, in whom DNA was sampled 34 months before diagnosis and again at the time of diagnosis. Shading represents cell populations defined by specific combinations of mutations as shown; the percentages refer to the estimated representation of each cell population in the sample, at initial DNA sampling and then at the time of diagnosis (34 months later).