title: Detection of R337H, a germline TP53 mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening program in Southern Brazil.
abstract: Germline TP53 mutations predispose to a rare familial cancer syndrome, the Li-Fraumeni Syndrome (LFS), characterized by the early onset of multiple cancers including childhood adrenocortical carcinomas, sarcomas and brain tumors, and breast and colon cancer in young adults. An identical germline mutation at codon 337 in TP53 (R337H) has been shown to be causally related to an increased risk of multiple cancers in unrelated subjects with familial cancer risk in Southern Brazil. Here we have assessed the prevalence of R337H in 750 healthy women participating in a community-based breast cancer screening program in the area of Porto Alegre. The mutant was detected in two participants (0.3%) who were fourth-degree relatives and reported a familial history of cancer at multiple sites that did not match classical criteria for LFS and its variants. Testing in additional family members detected the mutation in three subjects, one of whom developed breast cancer at the age of 36. These findings indicate that R337H may be a low penetrance mutant which predisposes to multiple cancers and occurs in the population of Southern Brazil at a frequency 10-20 times higher than other TP53 mutants commonly associated with LFS.
authors.affiliation: Post-Graduate Program in Genetics and Molecular Biology, Federal University of Rio Grande do Sul, Brazil.
authors.forename: Edenir Inêz
authors.initials: EI
authors.lastname: Palmero
authors.forename: Lavínia
authors.initials: L
authors.lastname: Schüler-Faccini
authors.forename: Maira
authors.initials: M
authors.lastname: Caleffi
authors.forename: Maria Isabel Waddington
authors.initials: MI
authors.lastname: Achatz
authors.forename: Magali
authors.initials: M
authors.lastname: Olivier
authors.forename: Ghyslaine
authors.initials: G
authors.lastname: Martel-Planche
authors.forename: Virginie
authors.initials: V
authors.lastname: Marcel
authors.forename: Ernestina
authors.initials: E
authors.lastname: Aguiar
authors.forename: Juliana
authors.initials: J
authors.lastname: Giacomazzi
authors.forename: Ingrid Petroni
authors.initials: IP
authors.lastname: Ewald
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
mesh_terms: D000328:Adult; D000368:Aged; D001938:Brazil; D001943:Breast Neoplasms / Q000175:diagnosis; D005260:Female; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D010375:Pedigree