Germline variants of Brazilian women with breast cancer and detection of a novel pathogenic ATM deletion in early-onset breast cancer

BACKGROUND: It is estimated that 5-10% of breast cancer cases are hereditary. The identification of pathogenic germline variants allows individualized preventive health care, improvement of clinical management and genetic counseling. Studies in ethnically admixed Latin American populations have identified regions with increased frequency of deleterious variants in breast cancer predisposing genes. In this context, the Brazilian population exhibits great genetic heterogeneity, and is not well represented in international databases, which makes it difficult to interpret the clinical relevance of germline variants.

METHODS: We evaluated the frequency of pathogenic/likely pathogenic (P/LP) germline variants in up to 37 breast cancer predisposing genes, in a cohort of 105 breast and/or ovarian cancer Brazilian women referred to two research centers between 2014 and 2019.

RESULTS: A total of 22 patients (21%) were found to carry P/LP variants, and 16 VUS were detected in 15 patients (14.3%). Additionally, a novel pathogenic ATM intragenic deletion was identified in an early-onset breast cancer. We also detected a BRCA1 pathogenic variant (c.5074+2T>C) in higher frequency (10×) than in other studies with similar cohorts.

CONCLUSIONS: Our findings contribute to the characterization of the genetic background of breast cancer predisposition in the Brazilian population as a useful resource to discriminate between deleterious variants and VUS, thus enabling improvement in the preventive health care and clinical management of carriers.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:28

Enthalten in:

Breast cancer (Tokyo, Japan) - 28(2021), 2 vom: 25. März, Seite 346-354

Sprache:

Englisch

Beteiligte Personen:

Bandeira, Gabriel [VerfasserIn]
Rocha, Katia [VerfasserIn]
Lazar, Monize [VerfasserIn]
Ezquina, Suzana [VerfasserIn]
Yamamoto, Guilherme [VerfasserIn]
Varela, Monica [VerfasserIn]
Takahashi, Vanessa [VerfasserIn]
Aguena, Meire [VerfasserIn]
Gollop, Thomaz [VerfasserIn]
Zatz, Mayana [VerfasserIn]
Passos-Bueno, Maria Rita [VerfasserIn]
Krepischi, Ana [VerfasserIn]
Okamoto, Oswaldo Keith [VerfasserIn]

Links:

Volltext

Themen:

ATM
ATM protein, human
Ataxia Telangiectasia Mutated Proteins
BRCA1
BRCA1 Protein
BRCA1 protein, human
BRCA2
BRCA2 Protein
BRCA2 protein, human
Breast and ovarian cancer susceptibility
EC 2.7.11.1
Hereditary breast and ovarian cancer (HBOC)
Journal Article
Multicenter Study

Anmerkungen:

Date Completed 06.10.2021

Date Revised 06.10.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s12282-020-01165-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM315569255