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Poster Display session 1

4664 - Large genomic rearrangements in BRCA1 and BRCA2 genes in the Portuguese population.


28 Sep 2019


Poster Display session 1


Pathology/Molecular Biology

Tumour Site


Joao Pinto


Annals of Oncology (2019) 30 (suppl_5): v797-v815. 10.1093/annonc/mdz269


J.M. Pinto1, S. Santos2, S. Fragoso2, A. Luis3, A.I. Clara3, P. Rodrigues3, J. Parreira3, S. Bento3, P. Louro3, F. Vaz3

Author affiliations

  • 1 Medical Oncology Department, Hospital Beatriz Angelo-Loures, 1070-325 - Lisboa/PT
  • 2 Clínica De Risco Familiar; Unidade De Investigação Em Patobiologia Molecular;, Instituto Portuguès de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPOLFG EPE), 1099-023 - Lisbon/PT
  • 3 Clinica De Risco Familiar, Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E. (IPOLFG EPE), 1099-023 - Lisbon/PT


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Abstract 4664


BRCA1 and BRCA2 are the genes most frequently associated with hereditary breast and ovarian cancer (HBOC). Besides point mutations, BRCA1/2 large genomic rearrangements (LGR) have been observed, with different frequencies in specific populations. This study aims to update the frequency of BRCA1 and BRCA2 LGR in our population, as well as to characterize the gene distribution of these genetic events.


All high risk pts referred to our multidisciplinary program between 2000-2018 that consented on genetic testing were reviewed for BRCA1 and BRCA2 point pathogenic variants (several methodologies throughout the years including Conformation Sensitive Gel Electrophoresis; Conformation Sensitive Capillary Electrophoresis; Sanger Sequencing and Next Generation Sequencing) and LGR with Multiplex Ligation dependent Probe Amplification (MLPA).


3763 of 3901 index pts consented on genetic testing and 473 pts had 476 different pathogenic variants (PV). In 3 cases double germline PV were observed: BRCA1 (c.68_69delAG) and CHEK2 [c.(908 + 1_909-1)_(1095 + 1_1096-1)del]; ATM (c.8264_8268delATAAG) and PALB2 (c.751C>T); BRCA2 (c.156_157insAlu) and CHEK2 (c.593-1G>T). BRCA1 PV were detected in 151 pts with 24 LGR of these (15,9%) being detected by MLPA. The most frequent BRCA1 LGR was c. (4185 + 1_4186-1)_(4357 + 1_4358-1)dup (n = 8). BRCA2 PV were detected in 260 pts with 99 LGR: 92 pts with the Portuguese founder mutation c.156_157insAlu (detected by specific PCR or MLPA) and 7 pts with other LGR (detected by MLPA). The second most frequent BRCA2 LGR was c. (8632 + 1_8633-1)_(8754 + 1_8755-1)dup (n = 5). Nine CHEK2 PV were detected with the SALSA MLPA probemix P045 BRCA2/CHEK2: c.1100delC (8 pts) and c. (908 + 1_909-1)_(1095 + 1_1096-1)del (1pt). The total percentage of BRCA1 and BRCA2 LGR in our cohort was 26%. Excluding the Portuguese founder mutation c.156_157insAlu, the prevalence of LGR was 6,5%.


There is a high prevalence of LGR in the Portuguese population, mostly because of the Portuguese founder mutation c.156_157insAlu. Even if excluding this event, other LRG still account for 6,5% of the BRCA1 and BRCA2 pathogenic variants. These results emphasize the importance of testing LGR in all patients with high risk HBOC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.


Has not received any funding.


All authors have declared no conflicts of interest.

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