Search results for "Brea"

Integrative analysis of structural variations using short-reads and linked-reads yields highly specific and sensitive predictions.

2020

Genetic diseases are driven by aberrations of the human genome. Identification of such aberrations including structural variations (SVs) is key to our understanding. Conventional short-reads whole genome sequencing (cWGS) can identify SVs to base-pair resolution, but utilizes only short-range information and suffers from high false discovery rate (FDR). Linked-reads sequencing (10XWGS) utilizes long-range information by linkage of short-reads originating from the same large DNA molecule. This can mitigate alignment-based artefacts especially in repetitive regions and should enable better prediction of SVs. However, an unbiased evaluation of this technology is not available. In this study, w…

Epidemiology of fascioliasis in human endemic areas

2005

AbstractConsidered a secondary zoonotic disease until the mid-1990s, human fascioliasis is at present emerging or re-emerging in many countries, including increases of prevalence and intensity and geographical expansion. Research in recent years has justified the inclusion of fascioliasis in the list of important human parasitic diseases. At present, fascioliasis is a vector-borne disease presenting the widest known latitudinal, longitudinal and altitudinal distribution.Fasciola hepaticahas succeeded in expanding from its European original geographical area to colonize five continents, despite theoretical restrictions related to its biology and in turn dependent upon environmental and human…

Norovirus: The Burden of the Unknown

2018

Human noroviruses (HNoVs) are primarily transmitted by the fecal-oral route, either by person-to-person contact, or by ingestion of contaminated food or water as well as by aerosolization. Moreover, HNoVs significantly contribute to foodborne diseases being the causative agent of one-fifth of acute gastroenteritis worldwide. As a consequence of globalization, transnational outbreaks of foodborne infections are reported with increasing frequency. Therefore, in this review, state-of-the-art information regarding molecular procedures for human norovirus detection in food as well common food processing technologies have been summarized. Besides, the purpose of this chapter is to consolidate bas…

Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer

2020

Abstract HER2 mutations define a subset of metastatic breast cancers with a unique mechanism of oncogenic addiction to HER2 signaling. We explored activity of the irreversible pan-HER kinase inhibitor neratinib, alone or with fulvestrant, in 81 patients with HER2-mutant metastatic breast cancer. Overall response rate was similar with or without estrogen receptor (ER) blockade. By comparison, progression-free survival and duration of response appeared longer in ER+ patients receiving combination therapy, although the study was not designed for direct comparison. Preexistent concurrent activating HER2 or HER3 alterations were associated with poor treatment outcome. Similarly, acquisition of m…

Retrospective Proteomic Screening of 100 Breast Cancer Tissues.

2017

The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The specimens were selected from patients with invasive ductal carcinoma of the breast, the most frequent and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers potentially useful for clinical applications. The proteomic screening; by 2D-IPG and mass spectrometry; allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients; and proteins expressed sporadically among the same patients. Wit…

ΔNp63 drives metastasis in breast cancer cells via PI3K/CD44v6 axis

2016

P63 is a transcription factor belonging to the family of p53, essential for the development and differentiation of epithelia. In recent years, it has become clear that altered expression of the different isoforms of this gene can play an important role in carcinogenesis. The p63 gene encodes for two main isoforms known as TA and ΔN p63 with different functions. The role of these different isoforms in sustaining tumor progression and metastatic spreading however has not entirely been clarified. Here we show that breast cancer initiating cells express ΔNp63 isoform that supports a more mesenchymal phenotype associated with a higher tumorigenic and metastatic potential. On the contrary, the ma…

2017

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of…

Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome

2019

Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomer…

From “Cellular” RNA to “Smart” RNA: Multiple Roles of RNA in Genome Stability and Beyond

2018

Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA…

CLOVE: classification of genomic fusions into structural variation events

2017

Background A precise understanding of structural variants (SVs) in DNA is important in the study of cancer and population diversity. Many methods have been designed to identify SVs from DNA sequencing data. However, the problem remains challenging because existing approaches suffer from low sensitivity, precision, and positional accuracy. Furthermore, many existing tools only identify breakpoints, and so not collect related breakpoints and classify them as a particular type of SV. Due to the rapidly increasing usage of high throughput sequencing technologies in this area, there is an urgent need for algorithms that can accurately classify complex genomic rearrangements (involving more than …