TP53 and neoplasm: Given the complex genomic changes seen in the 2 patients with 2 pathogenic germline variants each (Figure 2C, D), we sought to determine if the germline variants contributed to this somatic genotype, or whether somatic TP53 pathogenic variants alone were a driver of this tumor profile.28 We used genome-wide LOH as a marker of genomic instability.29 Genome-wide LOH can occur as a result of copy-loss LOH or copy-neutral LOH with duplication of the remaining allele.