Fig. 3: Somatic LOH identified in three resected CCM lesions using snDNA-sequencing.

a In three out of 9 samples considered, we identified somatic LOH in cells with activating PIK3CA variants. All three identified the regions including the previously identified CCM variant. Each set of columns corresponds to the proportion of cells called as heterozygous for a germline SNV for cells with (orange) and without (teal) an activating variant in PIK3CA. Exact chromosomal location and rsids for all loci in graph are reported in Supplementary Data 5. b Top portion graphical representation of expected genotype when cells with a germline exon 2–10 deletion have an additional LOH event. Bottom shows in sample CCM 5078 all 5 germline dbSNP variants within the region of the germline CCM2 exon 2–10 deletion had no genotype called (all 5 missing in 9/12 PIK3CA cells), consistent with complete loss of CCM2 exons 2–10. Similarly, pathogenic variants in KRIT1 and CCM2 were enriched for homozygosity in PIK3CA variant cells in samples CCM 5015 (c) and CCM 5004 (d). ***p < 1e−4. *p < 0.01. p-values for a are generated using an unpaired, one-sided, ranked-sum Wilcoxon test that is Bonferonni corrected to account for multiple comparisons. Specific p-values are 2.28e−5 (CCM 5004 Chr7p), 1.38e−5 (CCM 5015 chr7q), 3.78e−8 and 7.8e−7 (CCM 5078 chrs7p and 7q, respectively). p-values for b determined using binomial test and p-value for c determined using two-tailed chi-squared test. Underlying data for bar charts included in source data.