Genomic rearrangements in BRCA1 and BRCA2: a literature review

Ewald, Ingrid Petroni; Ribeiro, Patrícia Lisbôa Izetti; Palmero, Edenir Inêz; Cossio, Silvia Liliana; Giugliani, Roberto; Ashton‐Prolla, Patrícia

doi:10.1590/s1415-47572009005000049

Cited by 98 publications

(78 citation statements)

References 57 publications

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“…Our results confirmed the higher prevalence of rearrangements in the BRCA1 gene versus the BRCA2 gene documented in previous reports (21)(22)(23)(24)(25).…”

Section: Discussionsupporting

confidence: 93%

Frequency of Rearrangements Versus Small Indels Mutations in BRCA1 and BRCA2 Genes in Turkish Patients with High Risk Breast and Ovarian Cancer

Yazıcı

Kilic

Akdeniz

et al. 2018

Eur J Breast Health

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IntroductionBreast cancer is the most common cancer among women worldwide and causes significant morbidity and mortality (1). According to the 2009 statistics of the Turkish Statistical Institute (TUIK), the leading cancer and the seventh-most-frequent cancer among women were breast and ovarian carcinoma, respectively. Among Turkish women, the incidence of breast cancer and ovarian carcinoma is 23% and 3.9%, respectively. Therefore, breast and ovarian carcinoma are important health problems for Turkish society. Furthermore, consanguineous marriages, especially among first cousins, are quite common in Turkey. This may lead to higher cancer risks, especially in families with cancer histories. It is very important to detect hereditary cancer risk using genetic testing for individuals in high-risk families as well as genetic testing, if applied correctly. Hence it is very important to determine the limits and content of genetic tests.Several factors increase the risk of breast cancer such as family history, reproductive history, diet, hormone use, radiation exposure, obesity, sedentary lifestyle, lack of breast-feeding, and exogenous hormone replacement therapy (1). Among these, a family history with breast and ovarian cancer in several generations is present in about 15-20% of all cases (2). Germline mutations of two major tumor suppressor genes, BRCA1 and BRCA2, are inherited in an autosomal dominant pattern and have links to breast and ovarian cancer (3). These two mutated genes increase the risk of breast cancer by 87% and 44% for ovarian cancer over the lifetime of female patients (4, 5). BRCA1 and BRCA2 participate in cellular functions such as cell growth, cell division, and genetic instability. Eur J Breast Health 2018; 14: 93-99 DOI: 10.5152/ejbh.2017.3799 93 ABSTRACT Objective: The current rearrangement ratio of BRCA1 and BRCA2 genes is not known in the Turkish population. Rearrangements are not routinely investigated in many Turkish laboratories. This creates problems and contradictions between clinics. Therefore, the aim of this study was to evaluate the distribution and frequency of rearrangements in BRCA1 and BRCA2 genes in high-risk families and to clarify the limits of BRCA1 and BRCA2 testing in Turkey. Frequency of Rearrangements Versus Materials and Methods:The study included 1809 patients at high risk of breast cancer or ovarian cancer. All patients were investigated for both small indels and rearrangements of BRCA genes using DNA sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis. Results:The overall frequency of rearrangements was 2% (25/1262). The frequency of rearrangements was 1.7% (18/1086) and 4% (9/206) in patients with breast cancer and ovarian cancer, respectively. The frequency of rearrangements was 3.7% (8/215) in patients with triple-negative breast cancer. The rearrangement rate was 7.7% (2/26) in patients with both breast and ovarian cancer. Conclusions:Rearrangements were found with high rates and were strongly associated with bilateral and triple-...

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“…Our results confirmed the higher prevalence of rearrangements in the BRCA1 gene versus the BRCA2 gene documented in previous reports (21)(22)(23)(24)(25).…”

Section: Discussionsupporting

confidence: 93%

Frequency of Rearrangements Versus Small Indels Mutations in BRCA1 and BRCA2 Genes in Turkish Patients with High Risk Breast and Ovarian Cancer

Yazıcı

Kilic

Akdeniz

et al. 2018

Eur J Breast Health

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“…The sensitivity of SSCP ranges from 50% to 96%, whereas CSGE and PTT are estimated to detect only 75% and 76% of the BRCA1 and BRCA2 variants, respectively [55].To establish the real prevalence of all mutations in the BRCA1 and BRCA2 genes in a population, ideally a complete BRCA analysis (i.e., complete sequencing and study of large rearrangements) should be performed. The prevalence of rearrangement variants varies significantly in different populations [56]. Large genomic rearrangements may account for up 21.4% of the variants in high risk patients from Latin America and the Caribbean [57].…”

Section: Discussionmentioning

confidence: 99%

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

Ossa

Torres

2016

The Oncologist

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Background. Numerous epidemiological factors affect the probability of developing breast or ovarian cancer, but no predictor is as determinant as inheriting a mutation in BRCA1 or BRCA2. The concept of the founder effect explains the reduced genetic variability in some populations, according to the theory that new populations can be formed from a reduced number of individuals, so the new population would carry only a small fraction of the genetic variability of the original population. The main purpose of this review is to provide an update on the state of the art in founder mutations and some recurrent mutations that have recently been described in Latin America. Methods. A literature search was performed in the electronic databases of PUBMED, EMBASE, LILACS, and BIREME using the terms BRCA1, BRCA2, founder mutation, Latin American population, and Hispanic. Sixty-two papers were identified, of which 38 were considered relevant for this review. Each result is shown per country. Results. In Latin America, clear founder effects have been reported in Mexico (BRCA1 del exons 9-12), Brazil (BRCA1 5382insC and BRCA2 c.156_157insAlu), and Colombia (BRCA1 3450del4, A1708E, and BRCA2 3034del4) and in Latinas residing

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“…[7][8][9] Moreover, large genomic rearrangements (LGRs) of these genes require the use of other complementary techniques. 10,11 The development of cost-effective BRCA mutation detection workflows will not only benefit the genetic counseling process for patients with HBOCS but will also enhance the process of selecting patients for personalized treatments, as could be the case of PARP inhibitors, for example. Mutation analyses of BRCA1 and BRCA2 using NGS have been already performed for high-capacity NGS platforms, such as the 454 FLX (Roche), 12 the Helicos (Heliscope), 13 the Genome Analyzer (Illumina) 4 and, very recently, the GS Junior instrument.…”

Section: Introductionmentioning

confidence: 99%

Next-generation sequencing meets genetic diagnostics: development of a comprehensive workflow for the analysis of BRCA1 and BRCA2 genes

et al. 2012

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Next-generation sequencing (NGS) is changing genetic diagnosis due to its huge sequencing capacity and cost-effectiveness. The aim of this study was to develop an NGS-based workflow for routine diagnostics for hereditary breast and ovarian cancer syndrome (HBOCS), to improve genetic testing for BRCA1 and BRCA2. A NGS-based workflow was designed using BRCA MASTR kit amplicon libraries followed by GS Junior pyrosequencing. Data analysis combined Variant Identification Pipeline freely available software and ad hoc R scripts, including a cascade of filters to generate coverage and variant calling reports. A BRCA homopolymer assay was performed in parallel. A research scheme was designed in two parts. A Training Set of 28 DNA samples containing 23 unique pathogenic mutations and 213 other variants (33 unique) was used. The workflow was validated in a set of 14 samples from HBOCS families in parallel with the current diagnostic workflow (Validation Set). The NGS-based workflow developed permitted the identification of all pathogenic mutations and genetic variants, including those located in or close to homopolymers. The use of NGS for detecting copy-number alterations was also investigated. The workflow meets the sensitivity and specificity requirements for the genetic diagnosis of HBOCS and improves on the cost-effectiveness of current approaches.

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Genomic rearrangements in BRCA1 and BRCA2: a literature review

Cited by 98 publications

References 57 publications

Frequency of Rearrangements Versus Small Indels Mutations in BRCA1 and BRCA2 Genes in Turkish Patients with High Risk Breast and Ovarian Cancer

Frequency of Rearrangements Versus Small Indels Mutations in BRCA1 and BRCA2 Genes in Turkish Patients with High Risk Breast and Ovarian Cancer

Founder and Recurrent Mutations in BRCA1 and BRCA2 Genes in Latin American Countries: State of the Art and Literature Review

Next-generation sequencing meets genetic diagnostics: development of a comprehensive workflow for the analysis of BRCA1 and BRCA2 genes

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