Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice

// Angela Rosaria Solano 1,2 , Florencia Cecilia Cardoso 1 , Vanesa Romano 1 , Florencia Perazzo 3 , Carlos Bas 4 , Gonzalo Recondo 3 , Francisco Bernardo Santillan 5 , Eduardo Gonzalez 6 , Eduardo Abalo 7 , Maria Viniegra 8 , Jose Davalos Michel 9 , Lina Maria Nunez 10 , Cristina Maria Noblia 6 , Ignacio Mc Lean 11 , Enrique Diaz Canton 3 , Reinaldo Daniel Chacon 2 , Gustavo Cortese 12 , Eduardo Beccar Varela 11 , Martin Greco 3 , Maria Laura Barrientos 13 Silvia Adela Avila 14 , Hector Daniel Vuotto 5 , Antonio Lorusso 15 , Ernesto Jorge Podesta 2 and Oscar Gaspar Mando 16 1 Genotipificacion y Cancer Hereditario, Centro de Educacion Medicae Investigaciones Clinicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina 2 Instituto de Investigaciones Bioquimicas (INBIOMED), Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina 3 Servicio de Oncologia, Centro de Educacion Medicae Investigaciones Clinicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina 4 Hospital Aleman, Buenos Aires, Argentina 5 Sanatorio Mater Dei, Buenos Aires, Argentina 6 Mastologia, Instituto de Oncologia “Angel H. Roffo”, Universidad de Buenos Aires, Buenos Aires, Argentina 7 Instituto Universitario CEMIC, Buenos Aires, Argentina 8 Centro de Estudios de Estado y Sociedad (CEDES), Buenos Aires, Argentina 9 Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina 10 Genetica, Centro de Educacion Medicae Investigaciones Clinicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina 11 Centro Mamario, Hospital Universitario Austral, Buenos Aires, Argentina 12 Patologia Mamaria, Hospital de Clinicas “Jose de San Martin”, Buenos Aires, Argentina 13 Hospital Regional Victor M. Sanguinetti, Comodoro Rivadavia, Chubut, Escalante, Argentina 14 Hospital Provincial de Neuquen, Neuquen, Argentina 15 Liga Argentina de Lucha contra el Cancer (LALCEC), Buenos Aires, Argentina 16 DAM, Centro de Educacion Medicae Investigaciones Clinicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina Correspondence to: Angela Rosaria Solano, email: // Keywords : BRCA1/2 spectrum; BRCA1/2 recurrent mutations; Latin American BRCA1/2 mutations; hispanic panel; genetic testing policy Received : April 24, 2016 Accepted : July 10, 2016 Published : July 24, 2016 Abstract BRCA1/2 mutations in Latin America are scarcely documented and in serious need of knowledge about the spectrum of BRCA pathogenic variants, information which may alter clinical practice and subsequently improve patient outcome. In addition, the search for data on testing policies in different regions constitutes a fundamental strength for the present study, which analyzes BRCA1/2 gene sequences and large rearrangements in 940 probands with familial and/or personal history of breast/ovary cancer (BOC). In non-mutated DNA samples, Multiplex Ligation-dependent Probe Amplification assays (MLPA) were used for the analysis of large rearrangements. Our studies detected 179 deleterious mutations out of 940 (19.04%) probands, including 5 large rearrangements and 22 novel mutations. The recurrent mutations accounted for 15.08% of the total and only 2.87% of the probands analyzed, very different from a Hispanic panel previously described. In conclusion: a) this first comprehensive description of the spectrum in BRCA1/2 sheds light on the low frequency of recurrent mutations; b) this information is key in clinical practice to select adequate sequencing studies in our population, subsequently improve patient outcome and prevent damage associated to false normal reports resulting from the use of invalid population panels; c) panels of mutations from other populations should be cautiously validated before imported, even those of apparently similar origin, a concept to be considered beyond significance in Argentina.