Hereditary breast cancer in Middle Eastern and North African (MENA) populations: identification of novel, recurrent and founder BRCA1 mutations in the Tunisian population

Germ-line mutations in BRCA1 breast cancer susceptibility gene account for a large proportion of hereditary breast cancer families and show considerable ethnic and geographical variations. The contribution of BRCA1 mutations to hereditary breast cancer has not yet been thoroughly investigated in Middle Eastern and North African populations. In this study, 16 Tunisian high-risk breast cancer families were screened for germline mutations in the entire BRCA1 coding region and exon–intron boundaries using direct sequencing. Six families were found to carry BRCA1 mutations with a prevalence of 37.5%. Four different deleterious mutations were detected. Three truncating mutations were previously described: c.798_799delTT (916 delTT), c.3331_3334delCAAG (3450 delCAAG), c.5266dupC (5382 insC) and one splice site mutation which seems to be specific to the Tunisian population: c.212 + 2insG (IVS5 + 2insG). We also identified 15 variants of unknown clinical significance. The c.798_799delTT mutation occurred at an 18% frequency and was shared by three apparently unrelated families. Analyzing five microsatellite markers in and flanking the BRCA1 locus showed a common haplotype associated with this mutation. This suggests that the c.798_799delTT mutation is a Tunisian founder mutation. Our findings indicate that the Tunisian population has a spectrum of prevalent BRCA1 mutations, some of which appear as recurrent and founding mutations

Venezuela e ALBA: regionalismo contra-hegemônico e ensino superior para todos

Partindo de um quadro teórico neo-gramsciano crítico à globalização, este artigo aplica a nova teoria do regionalismo (NTR) e a teoria do regionalismo regulatório (TRR) à sua análise e teorização dos tratados de comércio da Aliança Bolivariana para os Povos da Nossa América (ALBA-TCP) como regionalismo contra-hegemônico na América Latina e Caribe (ALC). A ALBA está centrada na ideia de um Socialismo do Século XXI, que, como (inicialmente) também a Revolução Bolivariana da Venezuela, substitui a 'vantagem competitiva' pela 'vantagem cooperativa'. Em seu caráter de conjunto de processos multidimensionais e transnacionais a ALBA-TCP opera dentro de/transversalmente a um número de setores e escalas, ao mesmo passo que as transformações estruturais são movidas pela interação de agentes do Estado e agentes não estatais. A política de Educação Superior para Todos (ESPT) do governo venezuelano rejeita a agenda neoliberal globalizada de mercadorização, privatização e elitismo e reinvindica educação pública gratuita em todos os níveis como um direito humano fundamental. A ESPT está sendo regionalizado em um espaço educacional emergente da ALBA e assume um papel-chave nos processos de democracia direta e participatória, dos quais a construção popular (bottom-up) da contra-hegemonia e a redefinição política e econômica da ALC dependem. Antes de produzir sujeitos empreendedores conformes ao capitalismo global, a ESPT procura formar subjetividades ao longo de valores morais de solidariedade e cooperação. Isso será ilustrado com referência a um estudo etnográfico de caso da Universidade Bolivariana da Venezuela (UBV).This paper employs new regionalism theory and regulatory regionalism theory in its analysis and theorisation of the Bolivarian Alliance for the Peoples of Our America (ALBA) as a counter-hegemonic Latin American and Caribbean (LAC) regionalism. As (initially) the regionalisation of Venezuela's Bolivarian Revolution, ALBA is centred around the idea of a 21st Century Socialism that replaces the 'competitive advantage' with the 'cooperative advantage'. ALBA, as a set of multi-dimensional inter- and transnational processes, operates within and across a range of sectors and scales whilst the structural transformations are driven by the interplay of state and non-state actors. The Venezuelan government's Higher Education For All (HEFA) policy, which is being regionalised within an emergent ALBA education space, assumes a key role in the direct democratic and participatory democratic processes upon which a bottom-up construction of counter-hegemony depends. HEFA challenges the globalised neoliberal higher education agenda of commoditisation, privatisation and elitism. Rather than producing enterprising subjects fashioned for global capitalism, HEFA seeks to form subjectivities along the moral values of solidarity and cooperation

Immunolocalization of BRCA1 protein in tumor breast tissue: prescreening of BRCA1 mutation in Tunisian patients with hereditary breast cancer?

BRCA1 is a tumor suppressor gene which is inactivated by mutation in familial breast and ovarian cancers. Over 300 different disease causing germ-line mutations have been described; 60% are unique to an individual family. This diversity and the large size of the gene lead us to search for a pre-screening method for BRCA1 mutations. Since BRCA1 is a nuclear protein in normal cells, but reported by some authors to be cytoplasmic in breast tumor cells of patients with BRCA1 mutation, we evaluated immunohistochemistry as a prescreening technique to identify BRCA1 mutations in patients with familial presentation of breast cancer. Using a monoclonal antibody against the carboxy-terminal region of BRCA1, we performed immunohistochemistry on 18 tumor samples from patients with hereditary breast cancer. Cytoplasmic staining of BRCA1 was observed in 10 cases. Of the 18 tumors, 12 (66%) showed either BRCA mutation or BRCA1 accumulation or both, indicating that BRCA1 function might be lost in breast tumor cells not only through mutation, but also via abnormal cytoplasmic location. The immunohistochemical test used in this study would not be efficient as a pre-screening method of deleterious mutations, but it appeared useful to investigate tumor physiology

Complete mutation screening and haplotype characterization of BRCA1 gene in Tunisian patients with familial breast cancer

Breast cancer, the most commonly diagnosed cancer in women, is the second leading cause of cancer death in women worldwide. To investigate the contribution of BRCA1 gene mutations to familial breast cancer in Tunisia, 32 unrelated patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. BRCA1 mutation analysis was performed by DNA sequencing of all BRCA1 exons. We identified four different BRCA1 frameshift mutations: c. 4041delAG, c. 2551delG and c. 5266dupC already been described and one novel mutation, c. 211dupA, observed in two unrelated families. C. 5266dupC has previously been found among Jewish Ashkenazi and Eastern European populations. Our study describes it in Arabic/Berber population. Five out of thirty two familial cases had deleterious BRCA1 mutations. Fifteen additional cases carried unclassified variants (UV) or single nucleotide polymorphisms (SNPs). Our study is the first molecular investigation on the role of BRCA1 in hereditary breast cancer in North Tunisia