Extended Data Fig. 1: Genetic landscape of TP53-sAML.

a, Mutations, CNAs, TP53 VAF and allelic status identified in a cohort of 33 TP53-sAML patients by bulk sequencing. The barplot on the right indicates the frequency of each mutation in the cohort. The panel at the bottom indicates samples processed by TARGET-seq. b-c, Graphical representation of all CNAs identified by MoChA (b) and GISTIC analysis of recurrently lost (blue) and amplified (red) focal regions (c) in the same patients as in (b). In b, GISTIC q-values of arm-level gains (red) and loses (blue) are indicated for each chromosome arm. In c, TP53 chromosomal location is indicated in blue (17p13.1). d-g, Summary of CNA events spanning recurrently mutated genes TP53 (d), JAK2 (e), EZH2 (f) and TET2 (g), with evidence of deletion or loss of heterozygosity in the single-cell phylogenies computed in Extended Data Fig. 2b-o. For each gene, top panel shows a whole chromosome view and the bottom one, the gene-level view and RefSeq track. Points indicate the location of each point mutation and solid lines indicate CNA status (blue:loss; red:gain; green:LOH). h, Sanger sequencing of single-molecule patient-derived TP53 cDNA showing mutually exclusive alleles in the same cDNA molecule. i, VAF of TP53 mutations in patients in which at least two TP53 mutations were detected. Blue line represents the linear fit of the points, which deviates from the indicated slope that would be expected if mutations were on the same allele. When more than 2 mutations were present, the 2 with the highest VAF were analyzed. j, Contingency table of TP53 zygosity status in single cells from patients carrying two TP53 mutations. Double-mutant heterozygous cells are colored in red, mutually exclusive WT/homozygous or homozygous/WT genotypes in orange and homozygous/homozygous cells, in blue. “p” indicates exact one-sided binomial test p-value.