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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
Author(s) -
Magnusson Susanne,
Gisselsson David,
Wiebe Thomas,
Kristoffersson Ulf,
Borg Åke,
Olsson Håkan
Publication year - 2012
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.24223
Subject(s) - medicine , li–fraumeni syndrome , rhabdomyosarcoma , family history , germline mutation , cancer , breast cancer , population , incidence (geometry) , oncology , choroid plexus , sarcoma , mutation , pathology , genetics , physics , gene , optics , biology , central nervous system , environmental health
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. Pediatr Blood Cancer 2012; 59: 846–853. © 2012 Wiley Periodicals, Inc.