460 participants from 440 families were recruited through clinical genetics services in the UK (442 individuals), Greece (nine individuals), Hong Kong (three individuals), the US (three individuals), Israel (two individuals), and Ireland (one individual). In each family, there was a clinical suspicion of a cancer-predisposition syndrome, but routine genetic assessment and testing had not identified a germline molecular genetic diagnosis at the time of recruitment. 435 individuals had developed MPTs (defined here as at least two primaries by age 60 years or at least three by 70 years), and 25 had developed a single primary tumor and had a first-degree relative with MPTs. Tumors in the same tissue type and organ were considered separate primary tumors if, in the case of paired organs, they occurred bilaterally or if the medical record clearly denoted them as distinct. International Agency for Research on Cancer criteria for defining separate primaries were also used.8 Tumor diagnoses in the series were labeled according to site and cell of origin (Table S1).