The germline mutational landscape of BRCA1 and BRCA2 in Brazil

Author(s):Show less -

Palmero, Edenir Inez ^{[1, 2]} ; Carraro, Dirce Maria ^[3] ; Alemar, Barbara ^{[4, 5]} ; Martins Moreira, Miguel Angelo ^[6] ; Ribeiro-dos-Santos, Andrea ^{[7, 8]} ; Abe-Sandes, Kiyoko ^[9] ; Reis Galvao, Henrique Campos ^[10] ; Reis, Rui Manuel ^{[11, 1, 12]} ; Souza, Cristiano de Padua ^[10] ; Campacci, Natalia ^[1] ; Achatz, Maria Isabel ^[13] ; Brianese, Rafael Canfield ^[3] ; da Cruz Formiga, Maria Nirvana ^[14] ; Makdissi, Fabiana Baroni ^[15] ; Vargas, Fernando Regla ^{[16, 17]} ; Evangelista dos Santos, Anna Claudia ^[6] ; Seuanez, Hector N. ^[6] ; Lobo de Souza, Kelly Rose ^[6] ; Netto, Cristina B. O. ^[18] ; Santos-Silva, Patricia ^[5] ; da Silva, Gustavo Stumpf ^[5] ; Burbano, Rommel M. R. ^[19] ; Santos, Sidney ^{[7, 8]} ; Assumpcao, Paulo Pimentel ^[7] ; Monteiro Bernardes, Izabel Maria ^[7] ; Bonfim Machado-Lopes, Taisa Manuela ^[9] ; Bomfim, Thais Ferreira ^[9] ; Pereira Toralles, Maria Betania ^[9] ; Nascimento, Ivana ^{[9, 20]} ; Garicochea, Bernardo ^[21] ; Simon, Sergio D. ^[22] ; Noronha, Simone ^[23] ; de Lima, Fernanda Teresa ^[24] ; Chami, Anisse Marques ^{[25, 26]} ; Bittar, Camila Matzenbacher ^{[4, 5]} ; Bines, Jose ^[27] ; Artigalas, Osvaldo ^[28] ; Esteves-Diz, Maria Del Pilar ^[29] ; Petta Lajus, Tirzah Braz ^[30] ; Vieira Costa Gifoni, Ana Carolina Leite ^{[31, 32]} ; Guindalini, Rodrigo S. C. ^[33] ; Cintra, Terezinha Sarquis ^[34] ; Schwartz, Ida V. D. ^{[18, 4]} ; Bernardi, Pricila ^[35] ; Miguel, Diego ^[36] ; dos Santos Nogueira, Sonia Tereza ^[37] ; Herzog, Josef ^[38] ; Weitzel, Jeffrey N. ^[38] ; Ashton-Prolla, Patricia ^{[18, 4, 5]}

Affiliation:Show less -

^[1] Barretos Canc Hosp, Mol Oncol Res Ctr, Barretos - Brazil

^[2] Fac Ciencias Saude Barretos Dr Paulo Prata, Barretos Sch Hlth Sci, Barretos - Brazil

^[3] AC Camargo Canc Ctr, Int Res Ctr CIPE, Sao Paulo - Brazil

^[4] Univ Fed Rio Grande do Sul, Programa Posgrad Genet & Biol Mol, Porto Alegre, RS - Brazil

^[5] Hosp Clin Porto Alegre, Lab Med Genom, Porto Alegre, RS - Brazil

^[6] Inst Nacl Canc, Programa Genet, Rio De Janeiro - Brazil

^[7] Univ Fed Para, Programa Posgrad Genet & Biol Mol, Nucleo Pesquisas Oncol, Belem Do Para - Brazil

^[8] Univ Fed Para, Programa Posgrad Genet & Biol Mol, Lab Genet Humana & Med, Belem Do Para - Brazil

^[9] Univ Fed Bahia, Lab Imunol Biol Mol, Salvador, BA - Brazil

^[10] Barretos Canc Hosp, Dept Oncogenet, Barretos - Brazil

^[11] ICVS 3Bs PT Govt Associate Lab, Braga, Guimaraes - Portugal

^[12] Univ Minho, Hlth Sci Sch, Life & Hlth Sci Res Inst ICVS, Braga - Portugal

^[13] NCI, NIH, Clin Genet Branch, Hosp Sirio Libanes, Ctr Oncol, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD - USA

^[14] AC Camargo Canc Ctr, Oncogenet & Clin Oncol Dept, Sao Paulo - Brazil

^[15] AC Camargo Canc Ctr, Breast Surg Dept, Sao Paulo - Brazil

^[16] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Birth Defects Epidemiol Lab, Rio De Janeiro - Brazil

^[17] Univ Fed Estado Rio de Janeiro, Genet & Mol Biol Dept, Rio De Janeiro - Brazil

^[18] Hosp Clin Porto Alegre, Serv Genet Med, Porto Alegre, RS - Brazil

^[19] Hosp Ophir Loyola, Lab Biol Mol, Belem Do Para - Brazil

^[20] Nucleo Oncol Bahia, Grp Oncoclin, Salvador, BA - Brazil

^[21] Ctr Paulista Oncol, Oncoclin, Sao Paulo - Brazil

^[22] Hosp Israelita Albert Einstein, Dept Oncol Clin, Sao Paulo - Brazil

^[23] COAEM, Sao Paulo - Brazil

^[24] Hosp Israelita Albert Einstein, Ctr Aconselhamento Genet, Sao Paulo - Brazil

^[25] Rede Mater Dei de Saude, Belo Horizonte, MG - Brazil

^[26] Inst Hermes Pardini, Belo Horizonte, MG - Brazil

^[27] Oncopraxis, Rio De Janeiro - Brazil

^[28] HMV, Porto Alegre, RS - Brazil

^[29] Univ Sao Paulo, Fac Med, Inst Canc Estado Sao Paulo, Dept Radiol & Oncol, Sao Paulo - Brazil

^[30] Univ Fed Rio Grande do Norte, Hosp Liga Canc, Ctr Oncol Avancado CECAN, Serv Aconselhamento Genet, Dept Biol Celular & Gen, Natal, RN - Brazil

^[31] Rede DOr Fujiday & OncoStar, Fortaleza, Ceara - Brazil

^[32] Hosp Sao Carlos, Oncoctr, Fortaleza, Ceara - Brazil

^[33] CAM Grp, CLION, Salvador, BA - Brazil

^[34] Lab Genoma, Vitoria - Brazil

^[35] Univ Fed Santa Catarina, Div Clin Med, Hosp Univ, Serv Genet Med, Florianopolis, SC - Brazil

^[36] Univ Fed Bahia, Serv Genet Med, Hosp Univ Prof Edgard Santos, Salvador, BA - Brazil

^[37] Oncoclin Manaus, Dept Oncogenet, Manaus, Amazonas - Brazil

^[38] Dept Populat Sci, Div Clin Canc Genom City Hope, Duarte, CA - USA

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 8, JUN 15 2018.
• Web of Science Citations: 6

Abstract

The detection of germline mutations in BRCA1 and BRCA2 is essential to the formulation of clinical management strategies, and in Brazil, there is limited access to these services, mainly due to the costs/availability of genetic testing. Aiming at the identification of recurrent mutations that could be included in a low-cost mutation panel, used as a first screening approach, we compiled the testing reports of 649 probands with pathogenic/likely pathogenic variants referred to 28 public and private health care centers distributed across 11 Brazilian States. Overall, 126 and 103 distinct mutations were identified in BRCA1 and BRCA2, respectively. Twenty-six novel variants were reported from both genes, and BRCA2 showed higher mutational heterogeneity. Some recurrent mutations were reported exclusively in certain geographic regions, suggesting a founder effect. Our findings confirm that there is significant molecular heterogeneity in these genes among Brazilian carriers, while also suggesting that this heterogeneity precludes the use of screening protocols that include recurrent mutation testing only. This is the first study to show that profiles of recurrent mutations may be unique to different Brazilian regions. These data should be explored in larger regional cohorts to determine if screening with a panel of recurrent mutations would be effective. (AU)

• FAPESP's process: 13/24633-2 - Molecular characterization of at high risk families for hereditary breast cancer, negatives for BRCA1/BRCA2: looking for the BRCAx
• Grantee: Edenir Inêz Palmero
• Support Opportunities: Regular Research Grants