1415P - NGS and Sanger screening for BRCA1/BRCA2, CHEK2 and TP53 in argentinian high-risk breast/ovarian cancer families and bioinformatic studies: initial...

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancers in Adolescents and Young Adults (AYA)
Ovarian Cancer
Breast Cancer
Aetiology, Epidemiology, Screening and Prevention
Hereditary Syndromes
Basic Scientific Principles
Presenter Luisina Bruno
Citation Annals of Oncology (2017) 28 (suppl_5): v502-v506. 10.1093/annonc/mdx383
Authors L. Bruno1, P. Jablonski2, M. Ozkul2, G. Mercado3, J. Sendoya4, A. Llera4, L. Núñez5, R. Valdez6, D. Mansilla7, V. Cólica8, P. Kalfayan5, C. Ruggiero3, M. Reyes9, R. Cerretini2
  • 1Departamento De Oncología Clínica, Instituto Alexander Fleming, C1426ANZ - Ciudad Autónoma de Buenos Aires/AR
  • 2Departamento De Genética Experimental, Centro Nacional de Genética Médica, C1425ASQ - Ciudad Autónoma de Buenos Aires/AR
  • 3Departamento De Genética Clínica, Centro Nacional de Genética Médica, C1425ASQ - Ciudad Autónoma de Buenos Aires/AR
  • 4Consorcio Argentino De Tecnología Genómica, Fundación Instituto Leloir, Ciudad Autónoma de Buenos Aires/AR
  • 5Plan Nacional De Tumores Familiares Y Hereditarios, Instituto Nacional del Cáncer, Ciudad Autónoma de Buenos Aires/AR
  • 6Servicio De Oncología, Hospital Alemán, Ciudad Autónoma de Buenos Aires/AR
  • 7Departamento De Patología Mamaria, Instituto de Oncología Angel H. Roffo, Ciudad Autónoma de Buenos Aires/AR
  • 8Servicio De Oncología, Hospital Durand, Ciudad Autónoma de Buenos Aires/AR
  • 9Jefatura, Centro de Estudios Genéticos, Ciudad Autónoma de Buenos Aires/AR



In this study, we aimed at reporting the frequency of BRCA, CHEK2 and TP53 mutations in our high risk breast/ovarian cancer population, in order to determine the role of these genes testing in breast cancer risk assessment.


Total DNA of 484 unrelated cases and 180 relatives were sequence using either Sanger (564) or NGS (100) for BRCA1/BRCA2, CHEK2 and TP53 mutations. While 64.5% (312/484) of the population studied belong to jewish ethnicity, the remaining patients were european-amerindians.


Of the 484 probands analyzed, 15.9% were BRCA1/BRCA2 mutation carriers, 9.7% in BRCA1, 6% in BRCA2 and one patient was double heterozygous. Overall, 18.9% of the jewish patients presented ashkenazi founder mutations and 9.9% of european-amerindian population was positive for BRCA mutations. The c.66_67delAG was the most frequent alteration, representing 34.2% of all mutations identified. Pathogenic variants in CHEK2 and TP53 genes were present in 4% and 1.1% of our european-amerindian cases. Eighteen pathogenic variants different from ashkenazi panel were identified in BRCA, three were novel and twelve not previously reported in argentinian population. Twenty-seven variants of uncertain significance were found.


An association between genetic ancestry and mutational profile was observed only in the Jewish population. The 66.7% of the pathogenic variants found in our non-jewish cohort were in BRCA2. Our results confirm the high level of admixture present in argentinian population, and highlight the detection of novel variants that could be typical of our region. The knowledge of them is relevant to improve patient risk assessment.

Clinical trial identification

Legal entity responsible for the study

Centro Nacional de Genética Médica, ANLIS, Malbrán, Ministerio de Salud de la Nación




All authors have declared no conflicts of interest.