title: TP53 and CDKN1A mutation analysis in families with Li-Fraumeni and Li-Fraumeni like syndromes.
abstract: Li-Fraumeni and Li-Fraumeni like syndromes (LFS/LFL) represent rare cancer-prone conditions associated mostly with sarcomas, breast cancer, brain tumors, and adrenocortical carcinomas. TP53 germline mutations are present in up to 80 % of families with classic Li-Fraumeni syndrome, and in 20-60 % of families with Li-Fraumeni like phenotypes. The frequency of LFS/LFL families with no TP53 mutations detected suggests the involvement of other genes in the syndrome. In this study, we searched for mutations in TP53 in 39 probands from families with criteria for LFS/LFL. We also searched for mutations in the gene encoding the main mediator of p53 in cell cycle arrest, CDKN1A/p21, in all patients with no mutations in TP53. Eight probands carried germline disease-causing mutations in TP53: six missense mutations and two partial gene deletions. No mutations in CDKN1A coding region were detected. TP53 partial deletions in our cohort represented 25 % (2/8) of the mutations found, a much higher frequency than usually reported, emphasizing the need to search for TP53 rearrangements in patients with LFS/LFL phenotypes. Two benign tumors were detected in two TP53 mutation carriers: an adrenocortical adenoma and a neurofibroma, which raises a question about the possible implication of TP53 mutations on the development of such lesions.
authors.affiliation: Genetics Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Raissa Coelho
authors.initials: RC
authors.lastname: Andrade
authors.affiliation: Genetics Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Anna Claudia Evangelista
authors.initials: AC
authors.lastname: Dos Santos
authors.affiliation: Clínica de Oncologia Pediátrica da Santa Casa de Belo Horizonte, Belo Horizonte, Brazil.
authors.forename: Joaquim Caetano
authors.initials: JC
authors.lastname: de Aguirre Neto
authors.affiliation: INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ-CIBERER, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Nevado
authors.affiliation: INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ-CIBERER, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
authors.affiliation: Genetics Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. fernando.vargas@ioc.fiocruz.br.|Genetics and Molecular Biology Department, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, Brazil. fernando.vargas@ioc.fiocruz.br.|Birth Defects Epidemiology Laboratory, Fundação Oswaldo Cruz, Av. Brasil 4365 - Pavilhão Leônidas Deane Sala 617, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil. fernando.vargas@ioc.fiocruz.br.
authors.forename: Fernando Regla
authors.initials: FR
authors.lastname: Vargas
mesh_terms: D018268:Adrenocortical Carcinoma / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics; D015331:Cohort Studies; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D060885:Multiplex Polymerase Chain Reaction; D020125:Mutation, Missense; D009455:Neurofibroma / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: CDKN1A; Gene deletion; Li–Fraumeni like syndrome; Li–Fraumeni syndrome; TP53