PMID- 28947987 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 1949-2553 (Electronic) IS - 1949-2553 (Linking) VI - 8 IP - 36 DP - 2017 Sep 1 TI - Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice. PG - 60487-60495 LID - 10.18632/oncotarget.10814 [doi] AB - 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. FAU - Solano, Angela Rosaria AU - Solano AR AD - Genotipificacion y Cancer Hereditario, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. AD - Instituto de Investigaciones Bioquimicas (INBIOMED), Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Cardoso, Florencia Cecilia AU - Cardoso FC AD - Genotipificacion y Cancer Hereditario, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. FAU - Romano, Vanesa AU - Romano V AD - Genotipificacion y Cancer Hereditario, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. FAU - Perazzo, Florencia AU - Perazzo F AD - Servicio de Oncologia, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. FAU - Bas, Carlos AU - Bas C AD - Hospital Aleman, Buenos Aires, Argentina. FAU - Recondo, Gonzalo AU - Recondo G AD - Servicio de Oncologia, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. FAU - Santillan, Francisco Bernardo AU - Santillan FB AD - Sanatorio Mater Dei, Buenos Aires, Argentina. FAU - Gonzalez, Eduardo AU - Gonzalez E AD - Mastologia, Instituto de Oncologia "Angel H. Roffo", Universidad de Buenos Aires, Buenos Aires, Argentina. FAU - Abalo, Eduardo AU - Abalo E AD - Instituto Universitario CEMIC, Buenos Aires, Argentina. FAU - Viniegra, Maria AU - Viniegra M AD - Centro de Estudios de Estado y Sociedad (CEDES), Buenos Aires, Argentina. FAU - Michel, Jose Davalos AU - Michel JD AD - Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. FAU - Nunez, Lina Maria AU - Nunez LM AD - Genetica, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. FAU - Noblia, Cristina Maria AU - Noblia CM AD - Mastologia, Instituto de Oncologia "Angel H. Roffo", Universidad de Buenos Aires, Buenos Aires, Argentina. FAU - Mc Lean, Ignacio AU - Mc Lean I AD - Centro Mamario, Hospital Universitario Austral, Buenos Aires, Argentina. FAU - Canton, Enrique Diaz AU - Canton ED AD - Servicio de Oncologia, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. FAU - Chacon, Reinaldo Daniel AU - Chacon RD AD - Instituto de Investigaciones Bioquimicas (INBIOMED), Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Cortese, Gustavo AU - Cortese G AD - Patologia Mamaria, Hospital de Clinicas "Jose de San Martin", Buenos Aires, Argentina. FAU - Varela, Eduardo Beccar AU - Varela EB AD - Centro Mamario, Hospital Universitario Austral, Buenos Aires, Argentina. FAU - Greco, Martin AU - Greco M AD - Servicio de Oncologia, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. FAU - Barrientos, Maria Laura AU - Barrientos ML AD - Hospital Regional Victor M. Sanguinetti, Comodoro Rivadavia, Chubut, Escalante, Argentina. FAU - Avila, Silvia Adela AU - Avila SA AD - Hospital Provincial de Neuquen, Neuquen, Argentina. FAU - Vuotto, Hector Daniel AU - Vuotto HD AD - Sanatorio Mater Dei, Buenos Aires, Argentina. FAU - Lorusso, Antonio AU - Lorusso A AD - Liga Argentina de Lucha contra el Cancer (LALCEC), Buenos Aires, Argentina. FAU - Podesta, Ernesto Jorge AU - Podesta EJ AD - Instituto de Investigaciones Bioquimicas (INBIOMED), Facultad de Medicina, Universidad de Buenos Aires-CONICET, Buenos Aires, Argentina. FAU - Mando, Oscar Gaspar AU - Mando OG AD - DAM, Centro de Educacion Medicae Investigaciones Clinicas "Norberto Quirno" (CEMIC), Buenos Aires, Argentina. LA - eng PT - Journal Article DEP - 20160724 PL - United States TA - Oncotarget JT - Oncotarget JID - 101532965 PMC - PMC5601155 OTO - NOTNLM OT - BRCA1/2 recurrent mutations OT - BRCA1/2 spectrum OT - Latin American BRCA1/2 mutations OT - genetic testing policy OT - hispanic panel COIS- CONFLICTS OF INTERESTS The authors declare no competing interests EDAT- 2016/07/24 00:00 MHDA- 2016/07/24 00:01 PMCR- 2017/09/01 CRDT- 2017/09/27 06:00 PHST- 2016/04/24 00:00 [received] PHST- 2016/07/10 00:00 [accepted] PHST- 2017/09/27 06:00 [entrez] PHST- 2016/07/24 00:00 [pubmed] PHST- 2016/07/24 00:01 [medline] PHST- 2017/09/01 00:00 [pmc-release] AID - 10814 [pii] AID - 10.18632/oncotarget.10814 [doi] PST - epublish SO - Oncotarget. 2016 Jul 24;8(36):60487-60495. doi: 10.18632/oncotarget.10814. eCollection 2017 Sep 1.