PURPOSE: A clinical testing cohort was used to gain a broader understanding of 
the spectrum of tumors associated with germline p53 mutations to aid clinicians 
in identifying high-risk families.
PATIENTS AND METHODS: Full sequencing of the coding exons (2 to 11) and 
associated splice junctions of the p53 gene was performed on 525 consecutive 
patients whose blood samples were submitted for diagnostic testing. Clinical 
features of p53 germline carriers in this cohort were characterized, clinical 
referral schemes based on reported p53-associated family phenotypes were 
evaluated, and practical mutation prevalence tables were generated.
RESULTS: Mutations were identified in 91 (17%) of 525 patients submitted for 
testing. All families with a p53 mutation had at least one family member with a 
sarcoma, breast, brain, or adrenocortical carcinoma (ACC). Every individual with 
a choroid plexus tumor (eight of eight) and 14 of 21 individuals with a 
childhood ACC had a mutation regardless of family history. Based on reported 
personal and family history, 95% of patients (71 of 75) 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.
CONCLUSION: This is, to our knowledge, the largest single report of diagnostic 
testing for germline p53 mutations, yielding practical mutation prevalence 
tables and suggesting clinical utility of classic LFS and Chompret criteria for 
identifying a subset of cancer-prone families with p53 germline mutations, with 
important implications for diagnosis and management.