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01-12-2009

TP53 germline mutations in Portugal and genetic modifiers of age at cancer onset

Authors: Carla Pinto, Isabel Veiga, Manuela Pinheiro, Ana Peixoto, Armando Pinto, José M. Lopes, Rui M. Reis, Carla Oliveira, Manuela Baptista, Lúcia Roque, Fernando Regateiro, Luís Cirnes, Robert M. W. Hofstra, Raquel Seruca, Sérgio Castedo, Manuel R. Teixeira

Published in: Familial Cancer | Issue 4/2009

Abstract

The Li-Fraumeni syndrome (LFS) is a rare, autosomal dominant disease caused by TP53 germline mutations. This study aimed to characterize the TP53 mutational spectrum in patients suspected to have LFS in Portugal and to evaluate the influence of the MDM2-SNP309 and TP53-72Arg variants and of telomere length on age of tumor onset. Probands were primarily selected using the classical LFS criteria (two cases) or the more sensitive Chompret Li-Fraumeni-like (LFL) criteria (13 cases), but 12 additional patients that did not comply with those LFS or LFL criteria were included in the analysis based on clinical suspicion (LFS suspects). Nine of the 27 probands (33.3%) presented germline TP53 mutations, two of them occurring de novo and two of them being novel. Three of the nine TP53 mutations were found in families that did not comply with any of the commonly used criteria for TP53 testing, leaving room to recommend the use of less stringent criteria. An association was found between the presence of the TP53-72Arg (but not the MDM2-SNP309) variant and earlier age of onset in TP53 carriers. A negative correlation between telomere length and age of cancer onset was found in patients with germline TP53 mutation, whereas no such correlation was found in controls or in patients with wild-type TP53.

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Title: TP53 germline mutations in Portugal and genetic modifiers of age at cancer onset
Authors: Carla Pinto
Isabel Veiga
Manuela Pinheiro
Ana Peixoto
Armando Pinto
José M. Lopes
Rui M. Reis
Carla Oliveira
Manuela Baptista
Lúcia Roque
Fernando Regateiro
Luís Cirnes
Robert M. W. Hofstra
Raquel Seruca
Sérgio Castedo
Manuel R. Teixeira
Publication date: 01-12-2009
Publisher: Springer Netherlands
Published in: Familial Cancer / Issue 4/2009
Print ISSN: 1389-9600
Electronic ISSN: 1573-7292
DOI: https://doi.org/10.1007/s10689-009-9251-y

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