a, Diagrammatic representation of the integration of allele-specific copy number with purity and mutant allele frequencies to determine the zygosity of the germline pathogenic allele in the corresponding tumour (and the mechanism of its selection). CN-LOH, copy-neutral LOH. b, In only a subset of cases of low tumour cell content (<30%) does the LOH inference become increasingly analytically challenging (increasing rate of indeterminant calls). c, The percentage of cases with LOH affecting the germline pathogenic or somatic LoF BRCA1/2 mutations (as labelled) as a function of tumour purity (see Methods). Although somatic mutant allele frequencies are affected by tumour purity, this does not affect the sensitivity for LOH detection for germline variants and only affects sensitivity for LOH of somatic mutations in tumours of less than 30% purity. Error bars are 95% confidence intervals in all panels. d, In tumours with benign germline variants in BRCA1 and BRCA2, the ratio of zygosity changes affecting the wild-type or mutant BRCA1/2 allele is approximately 0.5, indicating neutral selection. By contrast, the rate of zygosity changes leading to loss of the wild-type allele in patients with germline pathogenic BRCA1 or BRCA2 mutations (>80%) is consistent with selective pressure for biallelic inactivation. e, Integrating all measurable sources of biallelic inactivation (inset, somatic sequence variants as the source of second hits to wild-type BRCA1/2), the percentage of tumours by cancer type containing a biallelic BRCA1 or BRCA2 loss. f, The rate of biallelic inactivation of BRCA1 versus BRCA2 in patients with germline pathogenic or somatic LoF mutations (in hypermutated and non-hypermutated tumours). P values determined by two-sided Fisher’s exact test. g, The rate of loss of wild-type BRCA1 or BRCA2 (LOH) in patients with germline deleterious BRCA1 or BRCA2 mutations compared with rare benign variants in either gene in BRCA-associated cancer types and in those not conventionally associated with BRCA germline carriers. P values determined by Fisher’s exact test. h, The rate of biallelic inactivation of BRCA1/2 in patients with germline pathogenic or somatic LoF mutations pan-cancer as a function of primary or metastatic specimen type. Right, the four BRCA-associated cancer types are shown individually. P values determined by two-sided Fisher’s exact test. ns, not significant. i, The rate of LOH spanning germline or somatic mutant BRCA1 and BRCA2 in breast cancers (coloured as in Fig. 2b, c) as well as other somatically mutated tumour-suppressor genes.