title: The Brazilian founder mutation TP53 p.R337H is uncommon in Portuguese women diagnosed with breast cancer.
abstract: Since the first studies reporting the TP53 p.R337H mutation as founder mutation in Southern and Southeastern Brazil, there has been controversy on its origin. Preliminary analysis of a small subset of Brazilian mutation carriers revealed that the haplotype incided on a Caucasian background. The vast majority of carriers identified today reside in Brazil or, if identified in other countries, are Brazilian immigrants. To our knowledge, the only two exceptions of carriers without a recognizable link with Brazil are two European families, from Portugal and Germany. Haplotype analysis in the Portuguese family revealed the same haplotype identified in Brazilian individuals, but in the German family, a distinct haplotype was found. Knowing that a significant proportion of women with breast cancer (BC) in Southern Brazil are p.R337H carriers, we analyzed p.R337H in a Portuguese cohort of women diagnosed with this disease. Median age at diagnosis among the first 573 patients tested was 60 years and 100 (17.4%) patients had been diagnosed at or under the age of 45 years. Mutation screening failed to identify the mutation in the 573 patients tested. These results are in contrast with the mutation frequency observed in a study including 815 BC-affected women from Brazil, in which carrier frequencies of 12.1 and 5.1% in pre- and postmenopausal women were observed, respectively. These findings suggest that the Brazilian founder mutation p.R337H, the most frequent germline TP53 mutation reported to date, is not a common germline alteration in Portuguese women diagnosed with BC.
authors: Genomic Medicine Laboratory, Experimental Research Centre, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Brazil; Genetics Department, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Hospital Tacchini, Bento Gonçalves, Brazil.
authors: Juliana
authors: J
authors: Giacomazzi
authors: Rudinei Luis
authors: RL
authors: Correia
authors: Edenir Ines
authors: EI
authors: Palmero
authors: Jorge Francisco
authors: JF
authors: Gaspar
authors: Marta
authors: M
authors: Almeida
authors: Catarina
authors: C
authors: Portela
authors: Suzi Alves
authors: SA
authors: Camey
authors: Augusta
authors: A
authors: Monteiro
authors: Manuela
authors: M
authors: Pinheiro
authors: Ana
authors: A
authors: Peixoto
authors: Manuel R
authors: MR
authors: Teixeira
authors: Rui Manuel
authors: RM
authors: Reis
authors: Patricia
authors: P
authors: Ashton-Prolla
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D011174:Portugal; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D044465:White People
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Li-Fraumeni Syndrome; Li-Fraumeni-Like Syndrome; TP53 gene and TP53 p.R337H mutation; breast cancer