Tumor Testing for Somatic and GermlineBRCA1/BRCA2Variants in Ovarian Cancer Patients in the Context of Strong Founder Effects

• Tipo: Artigo em Revista Científica Internacional
• Data: 2020

Autores

Peixoto, A (Autor) Outra; Pinto, P (Autor) Outra; Guerra, J (Autor) Outra; Pinheiro, M (Autor) Outra; Santos, C (Autor) Outra; Pinto, C (Autor) Outra; Santos, R (Autor) Outra; Escudeiro, C (Autor) Outra; Bartosch, C (Autor) Outra; Canario, R (Autor) Outra; Barbosa, A (Autor) Outra; Gouveia, A (Autor) Outra; Petiz, A (Autor) Outra; Abreu, MH (Autor) Outra; Sousa, S (Autor) Outra; Pereira, D (Autor) Outra; Silva, J (Autor) Outra; Manuel R Teixeira (Autor) ICBAS

Revista

Título: Frontiers in Oncology

Vol. 10

ISSN: 2234-943X

Editora: Frontiers Media

Indexação

ISI Web of Knowledge - 7 Citações

Scopus - 7 Citações

Outras Informações

ID Authenticus: P-00S-MRD

DOI: 10.3389/fonc.2020.01318

Abstract (EN): Deleterious variants in theBRCA1/BRCA2genes and homologous recombination deficiency (HRD) status are considered strong predictors of response to poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). The introduction of PARPi in clinical practice for the treatment of patients with advanced ovarian cancer imposed changes in the molecular diagnosis ofBRCA1/BRCA2variants.BRCA1/BRCA2tumor testing by next-generation sequencing (NGS) can detect simultaneously both somatic and germline variants, allowing the identification of more patients with higher likelihood of benefiting from PARPi. Our main goal was to determine the frequency of somatic and germlineBRCA1/BRCA2variants in a series of non-mucinous OC, and to define the best strategy to be implemented in a routine diagnostic setting for the screening of germline/somatic variants in these genes, including theBRCA2c.156_157insAlu Portuguese founder variant. We observed a frequency of 19.3% of deleterious variants, 13.3% germline, and 5.9% somatic. A higher prevalence of pathogenic variants was observed in patients diagnosed with high-grade serous ovarian cancer (23.2%). Considering the frequencies of the c.3331_3334del and the c.2037delinsCCBRCA1variants observed in this study (73% of allBRCA1pathogenic germline variants identified) and the limitations of NGS to detect theBRCA2c.156_157insAlu variant, it might be cost-effective to test for these founder variants with a specific test prior to tumor screening of the entire coding regions ofBRCA1andBRCA2by NGS in patients of Portuguese ancestry.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9