title: Prevalence of BRCA1/BRCA2 mutations in a Brazilian population sample at-risk for hereditary breast cancer and characterization of its genetic ancestry.
abstract: BACKGROUND
  There are very few data about the mutational profile of families at-risk for hereditary breast and ovarian cancer (HBOC) from Latin America (LA) and especially from Brazil, the largest and most populated country in LA.
  
  
  RESULTS
  Of the 349 probands analyzed, 21.5% were BRCA1/BRCA2 mutated, 65.3% at BRCA1 and 34.7% at BRCA2 gene. The mutation c.5266dupC (former 5382insC) was the most frequent alteration, representing 36.7% of the BRCA1 mutations and 24.0% of all mutations identified. Together with the BRCA1 c.3331_3334delCAAG mutation, these mutations constitutes about 35% of the identified mutations and more than 50% of the BRCA1 pathogenic mutations. Interestingly, six new mutations were identified. Additionally, 39 out of the 44 pathogenic mutations identified were not previously reported in the Brazilian population. Besides, 36 different variants of unknown significance (VUS) were identified. Regarding ancestry, average ancestry proportions were 70.6% European, 14.5% African, 8.0% Native American and 6.8% East Asian.
  
  
  METHODS
  This study characterized 349 Brazilian families at-risk for HBOC regarding their germline BRCA1/BRCA2 status and genetic ancestry.
  
  
  CONCLUSIONS
  This is the largest report of BRCA1/BRCA2 assessment in an at-risk HBOC Brazilian population. We identified 21.5% of patients harboring BRCA1/BRCA2 mutations and characterized the genetic ancestry of a sample group at-risk for hereditary breast cancer showing once again how admixed is the Brazilian population. No association was found between genetic ancestry and mutational status. The knowledge of the mutational profile in a population can contribute to the definition of more cost-effective strategies for the identification of HBOC families.
authors.affiliation: Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Gabriela C
authors.initials: GC
authors.lastname: Fernandes
authors.affiliation: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Rodrigo A D
authors.initials: RA
authors.lastname: Michelli
authors.affiliation: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Henrique C R
authors.initials: HC
authors.lastname: Galvão
authors.affiliation: Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: André E
authors.initials: AE
authors.lastname: Paula
authors.affiliation: Institute of Research and Innovation in Health, University of Porto, Porto, Portugal.|Institute of Molecular Pathology and Immunology at the University of Porto (IPATIMUP), Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Pereira
authors.affiliation: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Andrade
authors.affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Felicio
authors.affiliation: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Cristiano P
authors.initials: CP
authors.lastname: Souza
authors.affiliation: Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Deise R P
authors.initials: DR
authors.lastname: Mendes
authors.affiliation: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Sahlua
authors.initials: S
authors.lastname: Volc
authors.affiliation: Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Gustavo N
authors.initials: GN
authors.lastname: Berardinelli
authors.affiliation: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Rebeca S
authors.initials: RS
authors.lastname: Grasel
authors.affiliation: Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Cristina S
authors.initials: CS
authors.lastname: Sabato
authors.affiliation: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Danilo V
authors.initials: DV
authors.lastname: Viana
authors.affiliation: Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Prevention Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Edmundo C
authors.initials: EC
authors.lastname: Mauad
authors.affiliation: Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Pathology Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
authors.forename: Cristovam
authors.initials: C
authors.lastname: Scapulatempo-Neto
authors.affiliation: MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Banu
authors.initials: B
authors.lastname: Arun
authors.affiliation: Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal.|ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
authors.affiliation: Center of Molecular Diagnosis, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Oncogenetics Department, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.|Barretos School of Health Sciences, Dr. Paulo Prata-FACISB, São Paulo, Brazil.
authors.forename: Edenir I
authors.initials: EI
authors.lastname: Palmero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D040941:Heredity; D006801:Humans; D040582:Inheritance Patterns; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D055815:Young Adult
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor
keywords: BRCA1/BRCA2 mutation profile in Brazil; HBOC in brazil; c.5266dupC prevalence in brazil; genetic ancestry; hereditary breast cancer