title: A novel, de novo germline TP53 mutation in a rare presentation of the Li-Fraumeni syndrome in the maxilla.
abstract: We undertook the genetic analysis of a classic Li-Fraumeni syndrome (LFS) family with clustering of primary tumours including two maxillary sarcomas, a rare LFS site of tumour occurrence. Our aim was to investigate the presence of a specific type of TP53 mutation that could be associated with this unusual predilection of site for cancer occurrence. Mutational screening of the coding region of TP53 revealed an A>T transversion in codon 144 of exon 5 (CAG>CTG, Gln>Leu) in the germline of one of the three affected members, with loss of heterozygosity (LOH) in the tumour tissue. All other affected members were negative for germline or somatic TP53 mutations. TP53 immunohistochemistry was uninformative. The mutation we report is a de novo constitutional TP53 mutation that has not been previously described in the literature. It could explain the more burdened phenotype of the affected patient (died at 21 months). Alternative mechanisms to explain the overall family phenotype are discussed.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Eastman Dental Institute for Oral Health Care Sciences, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK. a.patrikidou@eastman.ucl.ac.uk
authors.forename: Anna
authors.initials: A
authors.lastname: Patrikidou
authors.forename: Jon
authors.initials: J
authors.lastname: Bennett
authors.forename: Patrick
authors.initials: P
authors.lastname: Abou-Sleiman
authors.forename: Joy D A
authors.initials: JD
authors.lastname: Delhanty
authors.forename: Malcolm
authors.initials: M
authors.lastname: Harris
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002813:Chondrosarcoma / Q000235:genetics; D005260:Female; D005784:Gene Amplification; D016158:Genes, p53; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007223:Infant; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D008441:Maxillary Neoplasms / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016159:Tumor Suppressor Protein p53