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

• Type: Article in International Scientific Journal
• Date: 2020

Authors

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

Journal

Title: Frontiers in Oncology

Vol. 10

ISSN: 2234-943X

Publisher: Frontiers Media

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 7 Citations

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9