Beyond Li-Fraumeni syndrome: Clinical characteristics of families with p53 germline mutations

11031 Background: Knowledge of the clinical spectrum of tumors associated with Li-Fraumeni Syndrome and p53 mutations is evolving with the availability of genotyping. A broader understanding of the phenotype and yield of clinical testing may inform candidates for testing. The objective of the current study is to identify features associated with p53 mutations in a clinical testing cohort in order to aid the clinician in identifying families with high risk for cancer, with important implications for diagnosis and management. Methods: Genetic analysis of p53 was performed, including full sequencing of the coding exons (2–11) and associated splice junctions, on 525 consecutive patients whose samples were submitted for diagnostic testing. Results: Mutations were identified in 91 of the 525 patients submitted for testing (17%). All families with a p53 mutation had at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma. Every individual with a choroid plexus tumor (9/9; 100%) and 67% of individuals with a childhood adrenocortical carcinoma (15/18) had a mutation regardless of family history. Based on reported personal and family history, 95% (71/75) of families with a mutation met either classic Li Fraumeni syndrome (LFS) or Chompret criteria. A simplified prevalence table provides a concise summary of individual and family characteristics associated with p53 mutations. Conclusions: Analysis of the largest single experience with diagnostic testing for germline p53 mutations yielded a practical mutation prevalence table, and suggests clinical utility of classic LFS and Chompret criteria, for identifying the subset of cancer-prone families with p53 germline mutations. No significant financial relationships to disclose.