Extended Data Fig. 8: Clonal architecture and chromosome 7 copy number inferred from single-cell DNA sequencing (scDNAseq).

Pattern of clonal evolution (created with BioRender.com) and visualization of genotypes of individual clones constructed from high quality single cells (allelic dropout rate <0.9) detected in 3 patients with SAMD9 (a, b) or SAMD9L (c) germline mutations. Mutational phylogeny was inferred from scDNAseq data using Tapestri Insights v2.2 and Mosaic packages. Root denotes the total number of cells analyzed for each sample and bolded circle symbolizes ancestral clone with germline SAMD9/9 L^mut. Percentage and number of single cells appear within colored circles; native state hematopoiesis (grey), second-site SAMD9L mutation (blue), UPD7q (green), -7 and -7 with somatic cancer mutations (both red). Variant allele frequency (VAF) from bulk sequencing is shown for reference. Panels (a) and (c) exemplify patients with branching evolution of independent benign and malignant SGR events arising from germline SAMD9/9 L^mut hematopoiesis. Panel (b) depicts the linear evolution of malignant -7 clone with SETBP1/ASXL1 mutation to acquire an additional MYB M375_I376dup mutation. Lower part of panels a–c depict the genotype annotation of the observed individual clones (shown above each genotype plot). Selected variants flanking SAMD9 or SAMD9L have either wildtype (WT), heterozygous (HET) or homozygous (HOM) genotype states. Right of lower panels show normalized amplicon read distribution of informative variants from scDNAseq, with red line marking the diploid state referenced from diploid cells.