title: A TP53 founder mutation, p.R337H, is associated with phyllodes breast tumors in Brazil.
abstract: A few studies have reported phyllodes tumors (PT) of the breast with germline TP53 mutations. Given this potential association and the high frequency of the TP53 p.R337H in southern and southeastern Brazil, the aim of this study was to assess whether p.R337H occurs among women diagnosed with such rare tumors in this region. Benign, borderline, and malignant breast PT were retrieved from eight pathology laboratories, and DNA was extracted from tumor tissue to perform p.R337H analysis. Overall, 128 cases classified as benign, 7 as borderline, and 13 as malignant PT were included in the study. The TP53 p.R337H mutation was identified in tumor cells of eight (5.4 %) cases. Analysis of DNA from non-tumoral tissue was possible in two of these, and both were p.R337H carriers in the germline. In addition, haplotype analysis was done in these two p.R337H carriers showing the presence of the founder haplotype previously reported in Brazilian mutation-positive individuals. Mutation frequency was significantly higher among malignant (3 of 13; 23 %) compared to benign tumors (5 of 128; 3.4 %) (p = 0.004). Mean age at PT diagnosis was not significantly different between mutation carriers and non-carriers. However, when subgroups where analyzed, the difference in age at diagnosis of carriers versus non-carriers within the group of benign tumors reached borderline significance. Our findings reinforce previous evidence that TP53 mutations have an important role in the development of both benign and malignant PT of the breast.
authors.affiliation: Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Rua Ramiro Barcelos, 2350, 90035-903 Porto Alegre, RS, Brazil. jugiacomazzi@gmail.com
authors.forename: Juliana
authors.initials: J
authors.lastname: Giacomazzi
authors.forename: Patricia
authors.initials: P
authors.lastname: Koehler-Santos
authors.forename: Edenir Inez
authors.initials: EI
authors.lastname: Palmero
authors.forename: Marcia S
authors.initials: MS
authors.lastname: Graudenz
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Rivero
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lima
authors.forename: Antonio Carlos Kruel
authors.initials: AC
authors.lastname: Pütten
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
authors.forename: Suzi Alves
authors.initials: SA
authors.lastname: Camey
authors.forename: Rodrigo Depieri
authors.initials: RD
authors.lastname: Michelli
authors.forename: Cristovam Scapulatempo
authors.initials: CS
authors.lastname: Neto
authors.forename: Mariana
authors.initials: M
authors.lastname: Fitarelli-Kiehl
authors.forename: Geraldo
authors.initials: G
authors.lastname: Geyer
authors.forename: Luise
authors.initials: L
authors.lastname: Meurer
authors.forename: Ana
authors.initials: A
authors.lastname: Geiger
authors.forename: Monica Blaya
authors.initials: MB
authors.lastname: Azevedo
authors.forename: Vinicius Duval
authors.initials: VD
authors.lastname: da Silva
authors.forename: Patricia
authors.initials: P
authors.lastname: Ashton-Prolla
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D016158:Genes, p53; D018095:Germ-Line Mutation; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D003557:Phyllodes Tumor / Q000235:genetics*