Haplotypic characterization of BRCA1 c.5266dupC, the prevailing mutation in Brazilian hereditary breast/ovarian cancer

Gomes, Rachel Novaes; Soares, Barbara L.; Felicio, Paula Silva; Michelli, Rodrigo Augusto Depieri; Netto, Cristina Brinckmann Oliveira; Alemar, Bárbara; Ashton‐Prolla, Patrícia; Palmero, Edenir Inêz; Moreira, Miguel Ângelo Martins

doi:10.1590//1678-4685-gmb-2019-0072

Cited by 11 publications

(10 citation statements)

References 19 publications

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“…To our knowledge, only two other Brazilian studies, with patients from the Northeast region, did not report this variant 37,49 . In fact, BRCA1 c.5266dupC (p.Gln1756fs) was reported in two previous studies with patients from our institution 50,51 , and by other studies with patients from Rio de Janeiro Estate 52 . The absence of BRCA1 c.5266dupC in the 257 patients analyzed here may reflect some differences to the cohort of patients studied by Lourenço et al 50 .…”

Section: Discussionsupporting

confidence: 58%

Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service

Matta

Gomes

Mattos

et al. 2022

Sci Rep

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Several studies have demonstrated the cost-effectiveness of genetic testing for surveillance and treatment of carriers of germline pathogenic variants associated with hereditary breast/ovarian cancer syndrome (HBOC). In Brazil, seventy percent of the population is assisted by the public Unified Health System (SUS), where genetic testing is still unavailable. And few studies were performed regarding the prevalence of HBOC pathogenic variants in this context. Here, we estimated the prevalence of germline pathogenic variants in BRCA1, BRCA2 and TP53 genes in Brazilian patients suspected of HBOC and referred to public healthcare service. Predictive power of risk prediction models for detecting mutation carriers was also evaluated. We found that 41 out of 257 tested patients (15.9%) were carriers of pathogenic variants in the analyzed genes. Most frequent pathogenic variant was the founder Brazilian mutation TP53 c.1010G > A (p.Arg337His), adding to the accumulated evidence that supports inclusion of TP53 in routine testing of Brazilian HBOC patients. Surprisingly, BRCA1 c.5266dupC (p.Gln1756fs), a frequently reported pathogenic variant in Brazilian HBOC patients, was not observed. Regarding the use of predictive models, we found that familial history of cancer might be used to improve selection or prioritization of patients for genetic testing, especially in a context of limited resources.

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Section: Discussionsupporting

confidence: 58%

Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service

Matta

Gomes

Mattos

et al. 2022

Sci Rep

Self Cite

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“…( 13), was identified in only 2 individuals in this study, corresponding to 6.4% of the P/LP BRCA1 variants. The small representation of this variant in the population of this study, from the Northeast Brazil, may be related to the fact that the immigration of Ashkenazi Jews from Central Europe during the 19th century occurred particularly to the Southeast and South regions of the country, where the mutation is nowadays more frequently described (25,26).…”

Section: Mutational Profilementioning

confidence: 81%

Hereditary Breast Cancer in the Brazilian State of Ceará (The CHANCE Cohort): Higher-Than-Expected Prevalence of Recurrent Germline Pathogenic Variants

Gifoni

Gifoni²,

Wotroba³

et al. 2022

Front. Oncol.

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PurposeThere is a significant lack of epidemiological data on hereditary cancer in Northeast Brazil. This is the largest study on the prevalence and mutational spectrum of cancer predisposition genes conducted in this region and the first in the State of Ceará.MethodsPatients ≥18 years of age that were referred to CHANCE (Grupo de Câncer Hereditário do Ceará) from March 2014 to December 2020 with testing criteria for breast cancer susceptibility genes according to NCCN v.1.2021 were eligible to participate. The inclusion of patients was limited to one individual per family and to those born in the State of Ceará. All patients underwent a hereditary cancer panel testing with at least 30 genes.ResultsA total of 355 patients were included, and 97 (27.3%) carried a P/LP germline variant in 18 different genes. Among the 97 P/LP carriers, BRCA1 (31, 31.9%) and BRCA2 (25, 25.7%) were the most frequently mutated genes, followed by PALB2 (10, 10.3%), CHEK2 (7, 7.2%) and ATM (4, 4.1%). A small number of recurrent variants (detected in three or more individuals) in BRCA1, BRCA2, CHEK2 and ATM represented the majority of the P/LP variants described in this cohort.ConclusionIn this cohort, the prevalence of L/PL was high, particularly involving the BRCA1, BRCA2, PALB2, CHEK2 and ATM genes and, to a lesser extent than expected, the TP53 gene. A high frequency of recurrent variants was also observed, for which further and larger analyses should clarify the presence of any possible founder effect. Characterizing the mutational profile of cancer predisposition genes in diverse populations may contribute to cancer prevention and therapeutic management.

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“…The c.5266dupC variant of BRCA 1 gene was the second most common mutation identified in BC patients from our study, being identified in 11 cases. This is a pathogenic mutation, located in the coding exon of the BRCA1 gene, which produces a frameshift insertion causing protein truncation and loss-of-function [ 11 ]. Although the c.5266dupC pathogenic variant was first described in Ashkenazi Jews, it was later identified in other populations from Europe and South America (Brazil) [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Spectrum of High-Risk Mutations among Breast Cancer Patients Referred for Multigene Panel Testing in a Romanian Population

Goidescu

Nemeti

Surcel

et al. 2023

Cancers

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(1) Background: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing (NGS) is becoming a standard in medical care. There are insufficient genetic studies reported on breast cancer (BC) patients from Romania and most of them are focused only on BRCA 1/2 genes (Breast cancer 1/2). (2) Methods: NGS was performed in 255 consecutive cases of BC referred for management in our clinic between 2015–2019. (3) Results: From the 171 mutations identified, 85 were in the high-penetrance BC susceptibility genes category, 72 were pathogenic genes, and 13 genes were in the (variants of uncertain significance) VUS genes category. Almost half of the mutations were in the BRCA 1 gene. The most frequent BRCA1 variant was c.3607C>T (14 cases), followed by c.5266dupC (11 cases). Regarding BRCA-2 mutations we identified c.9371A>T (nine cases), followed by c.8755-1G>A in three cases, and we diagnosed VUS mutations in three cases. We also identified six pathogenic variants in the PALB2 gene and two pathogenic variants in (tumor protein P 53) TP53. (4) Conclusions: The majority of pathogenic mutations in the Romanian population with BC were in the BRCA 1/ 2 genes, followed by PALB2 (partner and localizer of BRCA2) and TP53, while in the CDH1 (cadherin 1) and STK11 (Serine/Threonine-Protein Kinase) genes we only identified VUS mutations.

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Haplotypic characterization of BRCA1 c.5266dupC, the prevailing mutation in Brazilian hereditary breast/ovarian cancer

Cited by 11 publications

References 19 publications

Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service

Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service

Hereditary Breast Cancer in the Brazilian State of Ceará (The CHANCE Cohort): Higher-Than-Expected Prevalence of Recurrent Germline Pathogenic Variants

Spectrum of High-Risk Mutations among Breast Cancer Patients Referred for Multigene Panel Testing in a Romanian Population

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