Among these three tumors, there exist germline loss-of-function (LOF) mutations with somatic LOH in genes such as ATM, MRE11, FANCM, FANCI, WRN, and BRCA2. Notably, the increase in HRD in patient BC05 (Figure 2A) might be driven by the bi-allelic inactivation of WRN, where a mono-allelic germline alteration in the primary tumor progresses to the bi-allelic alteration by harboring a “second-hit” [20], somatic LOH in the relapsed tumor (see change from red to blue in WRN). The gene discussed is WRN; the disease is neoplasm.