title: TP53 mutations in primary breast carcinomas from white and African-Brazilian patients.
abstract: We have attempted to determine the incidence, nature and clinical significance of TP53 mutation in a group of white (242 cases) and African-Brazilian (52 cases) patients with breast cancer. The interethnic admixture as estimated by STR markers showed that white subjects displayed 67.9+/-0.4%, 25.0+/-1.7% and 7.0%+/-1.6% and the black populations had 34.4+/-1.9%, 56.2+/-1.9 and 9.4+/-2.2% respectively of European, African and Amerindian genes. Clinical parameters such as age, lymph node status and steroid receptors were similar in both groups. African-Brazilian patients presented more advanced lesions. Mutation screening was performed using polymerase chain reaction-single strand conformation analysis followed by sequencing. Compared to whites (13.6%), a relatively high frequency of TP53 mutation was found in blacks (32.7%) (p=0.001). African-Brazilian women have a larger proportion of mutations in exons 5 and 7, whereas white women have more mutations in exon 8. Mutations within exon 4 were found only in tumors of white patients. The spectra of TP53 mutations show that A:T-->G:C nucleotide transversion and G:C-->C:G transition were more common in African-Brazilian women whereas G:C-->T:A transversion occurs very frequently in whites. A high prevalence of G:C-->A:T nucleotide transitions and deletions was detected in both groups. No association was found between p53 gene mutation and tumor or clinical parameters independently of the ethnic group. With a median follow-up of 35.6 months for whites and 43.4 months for the blacks, no differences in overall survival were found. If white patients were stratified according to the type and location of TP53 mutations, patients with mutations affecting amino acids directly involved in DNA or Zn binding displayed a poor prognosis. The pattern of mutations found in our population seems to reflect a base line pattern observed in populations with similar ethnic profile with some modifications, which might be derived from specific etiological factors.
authors.affiliation: Departamento de Radiologia, Disciplina de Oncologia, Faculdade de Medicina, Universidade de São Paulo, Av, Dr. Arnaldo 455, 4o andar, Sala 4112, CEP-01246.903, São Paulo, Brazil.
authors.forename: Maria Aparecida
authors.initials: MA
authors.lastname: Nagai
authors.forename: Helenemarie
authors.initials: H
authors.lastname: Schaer Barbosa
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Zago
authors.forename: Wilson
authors.initials: W
authors.lastname: Araújo Silva
authors.forename: Inês Nobuko
authors.initials: IN
authors.lastname: Nishimoto
authors.forename: Sibeli
authors.initials: S
authors.lastname: Salaorni
authors.forename: Lívia Nery Franco
authors.initials: LN
authors.lastname: Guerreiro Costa
authors.forename: Marcos
authors.initials: M
authors.lastname: Silva Araújo
authors.forename: Ana Gabriela
authors.initials: AG
authors.lastname: Caldas Oliveira
authors.forename: Mário
authors.initials: M
authors.lastname: Mourâo Neto
authors.forename: Maria Mitzi
authors.initials: MM
authors.lastname: Brentani
mesh_terms: D000328:Adult; D000367:Age Factors; D044383:Black People; D001938:Brazil; D001943:Breast Neoplasms / Q000235:genetics*; D003062:Codon; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D016158:Genes, p53; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D017422:Sequence Analysis, DNA; D013997:Time Factors; D044465:White People
chemical_list: D003062:Codon