Extended Data Figure 10. Loss-of-heterozygosity event in MGH54 reveals two clones that span the cellular hierarchy.

a, Chromosome 18 loss of heterozygosity (LOH) in MGH54. Allelic fraction analysis of MGH54 SNPs from WES shows an imbalance (red and blue dots) in the frequency of alternative alleles in chromosome 1p, 19q, as well as chromosome 18, despite the normal copy number at this chromosome (Fig. 1a). This is consistent with an LOH event in which presumably one copy of chromosome 18 was deleted, and the other copy amplified. The weaker imbalance compared to chromosomes 1p and 19q further suggests that this is a subclonal event. b, Each of two clones defined by chromosome 18 LOH status spans the full hierarchy. Shown are the lineage (x axis) and stemness (y axis) scores for each cell from MGH54 (n = 1,174) classified as pre-LOH (red), post-LOH (blue) and unresolved (black) based on RNA-seq reads that map to SNPs in the minor (that is, deleted) chromosome. Both the pre- and post-LOH clones span the different tumour subpopulations. Pre-LOH cells were defined as all cells with reads that map to minor alleles in chromosome 18; post-LOH cells were defined as all cells with reads that map to at least five different major alleles, but no reads that map to minor alleles in chromosome 18; all other cells were defined as unresolved.