Two genes of greatest concern are TP53 (Li-Fraumeni syndrome) and CDH1 (hereditary diffuse gastric cancer), both of which are associated with high risks of cancer and management options that include prophylactic surgery and/or extensive, though often inadequate, surveillance.24,25 If a family without a classic phenotype is found to have a positive finding in either of these genes, the providers ordering the testing may question the appropriateness of applying standard management guidelines. The gene discussed is TP53; the disease is Li-Fraumeni syndrome.