Prevalence of germline TP53 mutations and history of Li-Fraumeni syndrome in families with childhood adrenocortical tumors, choroid plexus tumors, and rhabdomyosarcoma: a population-based survey.

PURPOSE: Whether childhood adrenocortical tumors (ACTs), choroid plexus tumors (CPTs), and rhabdomyosarcoma (RMS) are early manifestation of Li-Fraumeni syndrome (LFS) is uncertain. In this study, we evaluated the frequency of germline TP53 mutations and family history in a population-based series of patients.

PATIENTS AND METHODS: We identified children (≤18 years) diagnosed between 1958 and 2008 with ACT (n = 3) or CPT (n = 7), or children ≤5 years with RMS (n = 29). Registry-based pedigree expansion was performed.

RESULTS: No patients had a family history of classic LFS but 17 fulfilled Chompret or Eeles criteria. TP53 mutations were found in 1/3 ACT patients and 1/18 RMS patients; both were novel mutations. Of five tested CPT patients none had a detectable mutation. No excess of LFS associated tumors was observed, except for breast cancer in families of CPT patients. An overall increased cancer incidence was observed in families of patients with CPT [standardized incidence ratio (SIR) = 2.0; 95% CI: 1.1-3.5] due to excess of breast and female kidney cancer and in families of patients with RMS (SIR = 1.2; 95% CI: 0.9-1.7), due to excess of early-onset melanoma and male stomach cancer.

CONCLUSION: Relatives of patients with childhood ACTs, CPTs, and RMSs showed no increased risk of LFS associated tumors. However, TP53 mutations could be found in these children irrespective of family history. Absence of LFS associated tumors may suggest the presence of other cancer syndromes. Improved knowledge about relatives' cancer risks could be helpful in counseling family members of children with cancer.