Clinical Research Papers:

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 _, Florencia Cecilia Cardoso, Vanesa Romano, Florencia Perazzo, Carlos Bas, Gonzalo Recondo, Francisco Bernardo Santillan, Eduardo Gonzalez, Eduardo Abalo, María Viniegra, José Davalos Michel, Lina María Nuñez, Cristina Maria Noblia, Ignacio Mc Lean, Enrique Diaz Canton, Reinaldo Daniel Chacon, Gustavo Cortese, Eduardo Beccar Varela, Martín Greco, María Laura Barrientos, Silvia Adela Avila, Hector Daniel Vuotto, Antonio Lorusso, Ernesto Jorge Podesta and Oscar Gaspar Mando

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Oncotarget. 2017; 8:60487-60495. https://doi.org/10.18632/oncotarget.10814

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Angela Rosaria Solano1,2, Florencia Cecilia Cardoso1, Vanesa Romano1, Florencia Perazzo3, Carlos Bas4, Gonzalo Recondo3, Francisco Bernardo Santillan5, Eduardo Gonzalez6, Eduardo Abalo7, María Viniegra8, José Davalos Michel9, Lina María Nuñez10, Cristina Maria Noblia6, Ignacio Mc Lean11, Enrique Diaz Canton3, Reinaldo Daniel Chacon2, Gustavo Cortese12, Eduardo Beccar Varela11, Martín Greco3, María Laura Barrientos13 Silvia Adela Avila14, Hector Daniel Vuotto5, Antonio Lorusso15, Ernesto Jorge Podesta2 and Oscar Gaspar Mando16

1 Genotipificación y Cáncer Hereditario, Centro de Educación Médicae Investigaciones Clínicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina

2 Instituto de Investigaciones Bioquímicas (INBIOMED), Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina

3 Servicio de Oncología, Centro de Educación Médicae Investigaciones Clínicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina

4 Hospital Alemán, Buenos Aires, Argentina

5 Sanatorio Mater Dei, Buenos Aires, Argentina

6 Mastología, Instituto de Oncología “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 Genética, Centro de Educación Médicae Investigaciones Clínicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina

11 Centro Mamario, Hospital Universitario Austral, Buenos Aires, Argentina

12 Patología Mamaria, Hospital de Clínicas “José de San Martin”, Buenos Aires, Argentina

13 Hospital Regional Victor M. Sanguinetti, Comodoro Rivadavia, Chubut, Escalante, Argentina

14 Hospital Provincial de Neuquén, Neuquén, Argentina

15 Liga Argentina de Lucha contra el Cancer (LALCEC), Buenos Aires, Argentina

16 DAM, Centro de Educación Médicae Investigaciones Clínicas “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


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.

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