Extended Data Fig. 6: LOH associated signatures.
a) Association between LOH segments and mapped copy number signature segments across the full TCGA cohort. b) Recurrence of mapped LOH signatures (y-axis) across the genome in 1Mb bins (x-axis), split by LOH (blue) or heterozygous (orange) segments. Tumour suppressor genes with >20% of samples with LOH signatures are labelled. c) FACS sorting of undifferentiated sarcoma cells. Cells were gated on DAPI staining intensity (x-axis, proxy for DNA content), and ki67 intensity (y-axis, indicating replicating cells). Gates were chosen to isolate population of near haploid cells (~1n, green), replicating and non- replicating ~2n populations of cells (orange and purple respectively) and a ~4n population of cells (blue). d) Prevalence (orange line) and distribution (violins) of CN14 attributions across TCGA cancer types. Blue violins are cancer types significantly enriched in CN14 compared to all others (Q < 0.05, Mann Whitney test). KICH enrichment: OR = 4.6, P = 3.0e-3, Fisher’s exact test. ACC enrichment: OR = 8.9, P = 6.3e-9, Fisher’s exact test. e) Prevalence (orange line) and distribution (violins) of CN16 attributions across TCGA cancer types. Blue violins are cancer types significantly enriched in CN21 compared to all others (Q < 0.05, Mann Whitney test). KICH enrichment: OR = 30.5, P = 1.0e-21, Fisher’s exact test. ACC enrichment: OR = 37.4, P = 3.5e- 33, Fisher’s exact test. f) Recurrence of mapped arm-level LOH signatures (y-axis) across the genome in 1Mb bins (x-axis), split by LOH (blue) or heterozygous (orange) segments. Chromsome arms with >50% of samples with LOH signatures are labelled. g) Left: Heatmap of LOH prevalence by chromosome (x-axis) and sample (y-axis) for all CN13-CN16 attributed ACC, KICH or MESO samples. Samples are clustered according to chromosomal LOH levels. Right: Copy number signature attributions for the same samples. h) Recurrence of mapped chromosomal-scale and focal LOH signatures (y-axis) across the genome in 1Mb bins (x-axis), split by LOH (blue) or heterozygous (orange) segments. Chromosome arms with >20% of samples with LOH signatures are labelled. i) Enrichment of essential genes in regions of the genome with >20% of the samples having heterozygous segments of cLOH or fLOH signatures through bootstrapping of genomic regions.
