Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome

Ewald, Ingrid Petroni; Izetti, Patrícia; Vargas, Fernando; Moreira, Miguel A. M.; Moreira, Aline dos Santos; Moreira-Filho, Carlos Alberto; Cunha, D R; Hamaguchi, Sara Sumie Sobral; Camey, Suzi Alves; Schmidt, Aishameriane Venes; Caleffi, Maira; Koehler‐Santos, Patrícia; Giugliani, Roberto; Ashton‐Prolla, Patrícia

doi:10.1186/1897-4287-9-12

Cited by 39 publications

(26 citation statements)

References 41 publications

(48 reference statements)

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“…Haplotype characterization of Brazilian families from different ethnic backgrounds identified the same haplotype described in Ashkenazi Jews in other countries (Costa et al , 2008). An interesting phenotype, so far described only in a Brazilian cohort of HBOC families, is an apparent association of the BRCA1 c.5266dup mutation with an increased risk for bilateral breast cancer (Ewald et al , 2011). …”

Section: Resultsmentioning

confidence: 99%

Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

Ashton‐Prolla

Vargas

2014

Genet. Mol. Biol.

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Approximately 10% of all cancers are considered hereditary and are primarily caused by germline, high penetrance mutations in cancer predisposition genes. Although most cancer predisposition genes are considered molecularly heterogeneous, displaying hundreds of different disease-causing sequence alterations, founder mutations have been identified in certain populations. In some Latin American countries, founder mutations associated with increased risk of breast and other cancers have been described. This is particularly interesting considering that in most of these countries, populations are highly admixed with genetic contributions from native populations and from the in-flux of several distinct populations of immigrants. In this article, we present a review of the scientific literature on the subject and describe current data available on founder mutations described in the most common breast cancer predisposition genes: BRCA1, BRCA2 and TP53.

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Section: Resultsmentioning

confidence: 99%

Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

Ashton‐Prolla

Vargas

2014

Genet. Mol. Biol.

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“…This mutation is one of the most commonly found in Brazilian breast and/or ovarian cancer patients [11, 13, 32]. In addition, one meta-analysis reported that BRCA1 c.5266dupC is the fourth most prevalent in Latin America [33].…”

Section: Discussionmentioning

confidence: 99%

Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil

et al. 2016

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BackgroundApproximately 8–15% epithelial ovarian cancer patients are BRCA1 or BRCA2 germline mutation carriers. Brazilian inhabitants may have peculiar genetic characteristics associated with ethnic diversity, and studies focusing on the entire BRCA1/BRCA2 gene sequencing in Brazilian ovarian cancer patients are still lacking. The aim of this study was to evaluate BRCA1/2 mutations, through entire gene sequencing, in a Brazilian population of women with epithelial ovarian cancer.MethodsIn a cross sectional study performed in one reference centre for cancer treatment in São Paulo, Brazil, 100 patients diagnosed with epithelial ovarian cancer unselected for family history of breast and/or ovarian cancer were included. The complete coding sequence of BRCA1/2 genes was evaluated through Next-Generation or capillary sequencing. Large deletions were investigated through Multiplex Ligation-dependent Probe Amplification (MLPA).ResultsNineteen pathogenic mutations (BRCA1: n = 17 and BRCA2: n = 2) featuring 14 different mutations, including two large deletions in BRCA1 (exon 1–2 deleted and exon 5–7 deleted) were identified. Three mutations were detected more than once (c.3331_3334delCAAG, c.5266dupC and c.4484G > T). Two novel frameshift mutations were identified, one in BRCA1 (c.961_962delTG) and one in BRCA2 (c.1963_1963delC). BRCA1/2 mutations were seen in 35.5% of the patients with first and/or second-degree relatives with breast and/or ovarian cancer. Nineteen variants of uncertain significance (VUS) were detected (BRCA1: n = 2 and BRCA2: n = 17), including five distinct missense variants (BRCA1: c.5348 T > C; BRCA2: c.2350A > G, c.3515C > T, c.7534C > T, and c.8351G > A).ConclusionsAmong epithelial ovarian cancer patients unselected for family history of cancer, 19% were BRCA1/2 germline mutation carriers. Almost ¾ of the BRCA mutations, including two large deletions, were detected only once. Our work emphasizes the need of entire gene sequencing and MLPA screening in Brazil.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2966-x) contains supplementary material, which is available to authorized users.

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“…In Brazil, 6 studies that collectively screened 1151 individuals with hereditary BC reported 34 different BRCA mutations (24 in BRCA1 and 10 in BRCA2) [30][31][32][33][34][35], including 7 recurrent mutations (5 in BRCA1 and 2 in BRCA2) (Additional file 1: Table S1). In cohort B, a study by Carraro et al [36] (n = 54) detected another 5 mutations (2 in BRCA1 and 3 in BRCA2), including the recurrent mutation c.5266dupC (3.7%), which was also a recurrent mutation in hereditary BC (Additional file 1: Table S1).…”

Section: The Scope Of Brca1 and Brca2 Mutations In Central And South mentioning

confidence: 99%

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

et al. 2017

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Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate-and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35.

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Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome

Cited by 39 publications

References 41 publications

Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

Prevalence and impact of founder mutations in hereditary breast cancer in Latin America

Germline mutations in BRCA1 and BRCA2 in epithelial ovarian cancer patients in Brazil

Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations

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