Performance of BOADICEA and BRCAPRO genetic models and of empirical criteria based on cancer family history for predicting BRCA mutation carrier probabilities: A retrospective study in a sample of Italian cancer genetics clinics

Abstract Purpose To evaluate in current practice the performance of BOADICEA and BRCAPRO risk models and empirical criteria based on cancer family history for the selection of individuals for BRCA genetic testing. Patients and methods The probability of BRCA mutation according to the three tools was retrospectively estimated in 918 index cases consecutively undergone BRCA testing at 15 Italian cancer genetics clinics between 2006 and 2008. Results 179 of 918 cases (19.5%) carried BRCA mutations. With the strict use of the criteria based on cancer family history 173 BRCA (21.9%) mutations would have been detected in 789 individuals. At the commonly used 10% threshold of BRCA mutation carrier probability, the genetic models showed a similar performance [PPV (38% and 37%), sensitivity (76% and 77%) and specificity (70% and 69%)]. Their strict use would have avoided around 60% of the tests but would have missed approximately 1 every 4 carriers. Conclusion Our data highlight the complexity of BRCA testing referral in routine practice and question the strict use of genetic models for BRCA risk assessment

Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer.

Background: HER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients. Materials and methods: Using a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status. Results: One hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3-16.7). Conclusions: Co-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic

Skin, paper, tiles: a cross-cultural history of Kadiwéu art

This article focuses on the global traffic in images relating to Kadiwéu culture in South America, analyzing the extent to which they are entangled in the group’s continuing sense of presence. It begins with Kadiwéu designs as they appeared in the sketchbook of the artist-explorer Guido Boggiani in the late nineteenth century. It then explores the mapping of Kadiwéu territory and the practices and protocols informing a politics of land rights, cultural property and economic survival, looking in particular at the commissioning of Kadiwéu designs for a housing estate and an associated exhibition in Berlin early in the twentieth-first century. By developing a cross-cultural history of Kadiwéu art that considers the transnational networks across different times and spaces, including the case of a transcultural history of copyright, the article seeks to contribute to the ongoing re-thinking of the colonial archive and its afterlife

Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1(R132H) mutations. Patients harbouring IDH1(R132H) mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1(R132H) have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1(R132H) mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.MTG6Molecular tumour pathology - and tumour genetic

Arqueologia e história indígena no Pantanal

O artigo apresenta uma síntese dos dados arqueológicos sobre o Pantanal e o seu entorno, principalmente em Mato Grosso e Mato Grosso do Sul. Elaborado com base na noção de arqueologia como história indígena de longa duração, o artigo considera as trajetórias de estabelecimento e consolidação territorial da ocupação indígena regional, os processos de formação da configuração etnográfica encontrada pelos europeus e os impactos do colonialismo. O principal objetivo consiste em mostrar que a diversidade cultural característica do cenário etnográfico pantaneiro está associada à dinâmica histórica e cultural da ocupação indígena desde períodos anteriores à chegada dos conquistadores e colonizadores de origem europeia.The article presents an overview of the archaeological data on the Pantanal and its surrounding areas, mainly in Mato Grosso and Mato Grosso do Sul. Prepared based on the notion of archeology as long term indigenous history, the article considers the trajectories of territorial establishment and consolidation of the regional indigenous occupation, the formation processes of ethnographic setting found by Europeans and the impact of colonialism. The main objective is to show that cultural diversity characteristic of the Pantanal ethnographic scenario is associated with historical and cultural dynamics of indigenous occupation from periods prior to the arrival of the conquistadors and settlers of European origin