Prognostic value of CCND1 gene status in sporadic breast tumours, as determined by real-time quantitative PCR assays

The CCND1 gene, a key cell-cycle regulator, is often altered in breast cancer, but the mechanisms underlying CCND1 dysregulation and the clinical significance of CCND1 status are unclear. We used real-time quantitative PCR and RT–PCR assays based on fluorescent TaqMan methodology to quantify CCND1 gene amplification and expression in a large series of breast tumours. CCND1 overexpression was observed in 44 (32.8%) of 134 breast tumour RNAs, ranging from 3.3 to 43.7 times the level in normal breast tissues, and correlated significantly with positive oestrogen receptor status (P=0.0003). CCND1 overexpression requires oestrogen receptor integrity and is exacerbated by amplification at 11q13 (the site of the CCND1 gene), owing to an additional gene dosage effect. Our results challenge CCND1 gene as the main 11q13 amplicon selector. The relapse-free survival time of patients with CCND1-amplified tumours was shorter than that of patients without CCND1 alterations, while that of patients with CCND1-unamplified-overexpressed tumours was longer (P=0.011). Only the good prognostic significance of CCND1-unamplified-overexpression status persisted in Cox multivariate regression analysis. This study confirms that CCND1 is an ER-responsive or ER-coactivator gene in breast cancer, and points to the CCND1 gene as a putative molecular marker predictive of hormone responsiveness in breast cancer. Moreover, CCND1 amplification status dichotomizes the CCND1-overexpressing tumors into two groups with opposite outcomes

Geolocation with respect to persona privacy for the Allergy Diary app - a MASK study

Background: Collecting data on the localization of users is a key issue for the MASK (Mobile Airways Sentinel network: the Allergy Diary) App. Data anonymization is a method of sanitization for privacy. The European Commission's Article 29 Working Party stated that geolocation information is personal data. To assess geolocation using the MASK method and to compare two anonymization methods in the MASK database to find an optimal privacy method. Methods: Geolocation was studied for all people who used the Allergy Diary App from December 2015 to November 2017 and who reported medical outcomes. Two different anonymization methods have been evaluated: Noise addition (randomization) and k-anonymity (generalization). Results: Ninety-three thousand one hundred and sixteen days of VAS were collected from 8535 users and 54,500 (58. 5%) were geolocalized, corresponding to 5428 users. Noise addition was found to be less accurate than k-anonymity using MASK data to protect the users' life privacy. Discussion: k-anonymity is an acceptable method for the anonymization of MASK data and results can be used for other databases.Peer reviewe

The exon 13 duplication in the BRCA1 gene is a founder mutation present in geographicaly diverse populations

Recently, a 6-kb duplication of exon 13, which creates a frameshift in the coding sequence of the BRCA1 gene, has been described in three unrelated U.S. families of European ancestry and in one Portuguese family. Here, our goal was to estimate the frequency and geographic diversity of carriers of this duplication. To do this, a collaborative screening study was set up that involved 39 institutions from 19 countries and included 3,580 unrelated individuals with a family history of the disease and 934 early-onset breast and/or ovarian cancer cases. A total of 11 additional families carrying this mutation were identified in Australia (1), Belgium (1), Canada (1), Great Britain (6), and the United States (2). Haplotyping showed that they are likely to derive from a common ancestor, possibly of northern British origin. Our results demonstrate that it is strongly advisable, for laboratories carrying out screening either in English-speaking countries or in countries with historical links with Britain, to include within their BRCA1 screening protocols the polymerase chain reaction-based assay described in this report

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

Instrumentatio

INVOLVEMENT OF ELAV-LIKE PROTEINS IN SPATIAL LEARNING

International audienc

Cytosolic hippocampal PKC and aging: Correlation with discrimination performance

Adult and aged mice were submitted to a discrimination task in a radial maze (regular trials), and then to probe trials requiring them to form relational representations. Three weeks later, animals were again tested for regular and probe trials. Following another interval of 3 weeks, individual hippocampal cytosolic calcium-dependent and -independent PKC activities were measured. Performance of aged animals was impaired on probe but not regular trials and aged mice had lower hippocampal cytosolic calcium-dependent and - independent PKC activities than adults. Performance on probe trials was specifically correlated with calcium-dependent PKC activity. This suggests a specific relationship between the ability to form relational representations and hippocampal cytosolic calcium-dependent PKC activity