Development of a semi-conductor sequencing-based panel for genotyping of colon and lung cancer by the Onconetwork consortium.

Background: The number of predictive biomarkers that will be necessary to assess in clinical practice will increase with the availability of drugs that target specific molecular alterations. Therefore, diagnostic laboratories are confronted with new challenges: costs, turn-around-time and the amount of material required for testing will increase with the number of tests performed on a sample. Our consortium of European clinical research laboratories set out to test if semi-conductor sequencing provides a solution for these challenges.

First report of Kocuria marina spontaneous peritonitis in a child.

Background: Spontaneous bacterial peritonitis (SBP) is a rare affection in the pediatric population. It usually occurs when concurrent conditions are present, such as nephrotic syndrome, peritoneal dialysis or liver disease. We report a case of spontaneous bacterial peritonitis due to Kocuria marina in a 2-year-old child with no underlying risk factor.

Preclinical evaluation of dasatinib alone and in combination with cabozantinib for the treatment of diffuse intrinsic pontine glioma.

Background: Platelet-derived growth factor receptor A is altered by amplification and/or mutation in diffuse intrinsic pontine glioma (DIPG). We explored in vitro on new DIPG models the efficacy of dasatinib, a multi-tyrosine kinase inhibitor targeting this receptor.

Methods: Gene expression profiles were generated from 41 DIPGs biopsied at diagnosis and compared with the signature associated with sensitivity/resistance to dasatinib.

New insights on the mechanism of quinoline-based DNA Methyltransferase inhibitors.

Among the epigenetic marks, DNA methylation is one of the most studied. It is highly deregulated in numerous diseases, including cancer. Indeed, it has been shown that hypermethylation of tumor suppressor genes promoters is a common feature of cancer cells.

Impact of the lab-score on antibiotic prescription rate in children with fever without source: a randomized controlled trial.

Background: The Lab-score, based on the combined determination of procalcitonin, C-reactive protein and urinary dipstick results, has been shown accurate in detecting serious bacterial infections (SBI) in children with fever without source (FWS) on retrospective cohorts. We aimed to prospectively assess the utility of the Lab-score in safely decreasing antibiotic prescriptions in children with FWS and to determine its diagnostic characteristics compared to common SBI biomarkers.

Methods: Randomized controlled trial in children 7 days to 36 months old with FWS, allocated either to the Lab-score group (Lab-score reported, blinded WBC count) or to the control group (WBC, bands and C-reactive protein determined, blinded procalcitonin and Lab-score), followed up until recovery.

Tuning deposition of magnetic metallic nanoparticles from periodic pattern to thin film entrainment by dip coating method.

In this work, we report on the self-assembly of bimetallic CoFe carbide magnetic nanoparticles (MNPs) stabilized by a mixture of long chain surfactants. A dedicated setup, coupling dip coating and sputtering chamber, enables control of the self-assembly of MNPs from regular stripe to continuous thin films under inert atmosphere. The effects of experimental parameters, MNP concentration, withdrawal speed, amount, and nature of surfactants, as well as the surface state of the substrates are discussed.

Observed costs and health care use of children in a prospective cohort study on community-acquired pneumonia in Geneva, Switzerland.

Questions Under Study: Despite various efforts to estimate cost-effectiveness of pneumococcal conjugate vaccines, only scarce information on the cost burden of paediatric community acquired pneumonia (CAP) exists. The objective of this study was to prospectively calculate direct and indirect costs associated with treatment of CAP from a society perspective in children between 2 months and 16 years of age seeking care at a tertiary hospital in Geneva, Switzerland between December 2008 and May 2010.

Methods: This cost of illness study population comprised children aged from 2 months to 16 years of age seeking care for CAP at the University Children's Hospital Geneva from January 2008 through May 2010 (a subset of patients taken from a larger multicentre prospective cohort).

Genomes in the clinic: the Gustave Roussy Cancer Center experience.

The extensive molecular characterization of tumors with high throughput technologies has led to the segmentation of different tumors into very small molecularly defined subgroups. Many ongoing clinical trials are conducted only when specific molecular alterations are identified in tumor samples. In this review, we will describe the implementation of genome analysis in the clinical setting as it has expanded over the last four years in our Precision Medicine Program.

Overexpression of genes involved in miRNA biogenesis in medullary thyroid carcinomas with RET mutation.

Abnormal expression of non-coding micro RNA (miRNA) has been described in medullary thyroid carcinoma (MTC). Expression of genes encoding factors involved in miRNA biogenesis results often deregulated in human cancer and correlates with aggressive clinical behavior. In this study, expression of four genes involved in miRNA biogenesis (DICER, DROSHA, DCGR8, and XPO5) was investigated in 54 specimens of MTC.

Vemurafenib cooperates with HPV to promote initiation of cutaneous tumors.

Treatment with RAF inhibitors such as vemurafenib causes the development of cutaneous squamous cell carcinomas (cSCC) or keratoacanthomas as a side effect in 18% to 30% of patients. It is known that RAF inhibitors activate the mitogen-activated protein kinase (MAPK) pathway and stimulate growth of RAS-mutated cells, possibly accounting for up to 60% of cSCC or keratoacanthoma lesions with RAS mutations, but other contributing events are obscure. To identify such events, we evaluated tumors from patients treated with vemurafenib for the presence of human papilloma virus (HPV) DNA and identified 13% to be positive.

Comparative genomic hybridisation array and DNA sequencing to direct treatment of metastatic breast cancer: a multicentre, prospective trial (SAFIR01/UNICANCER).

Background: Breast cancer is characterised by genomic alterations. We did a multicentre molecular screening study to identify abnormalities in individual patients with the aim of providing targeted therapy matched to individuals' genomic alterations.

Methods: From June 16, 2011, to July 30, 2012, we recruited patients who had breast cancer with a metastasis accessible for biopsy in 18 centres in France.

Chromatin immunoprecipitation indirect peaks highlight long-range interactions of insulator proteins and Pol II pausing.

Eukaryotic chromosomes are partitioned into topologically associating domains (TADs) that are demarcated by distinct insulator-binding proteins (IBPs) in Drosophila. Whether IBPs regulate specific long-range contacts and how this may impact gene expression remains unclear. Here we identify "indirect peaks" of multiple IBPs that represent their distant sites of interactions through long-range contacts.

Small-cell carcinoma in the setting of pulmonary adenocarcinoma: new insights in the era of molecular pathology.

Introduction: Transformation into small-cell lung carcinoma (SCLC) has been reported as an evolution of lung adenocarcinoma acquiring resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI). However, spontaneous association of SCLC and adenocarcinoma also exists. We sought to compare patients' clinical features and mutation status of EGFR in each tumor component in these conditions.

Does KRAS mutational status predict chemoresistance in advanced non-small cell lung cancer (NSCLC)?

Background: Clinical implications of KRAS mutational status in advanced non-small cell lung cancer (NSCLC) remain unclear. To clarify this point, we retrospectively explored whether KRAS mutations could impact tumor response, and disease control rate (DCR) to first-line platinum-based chemotherapy (CT) as well as progression-free survival (PFS) or overall survival (OS).

Methods: Between June 2009 and June 2012, 340 patients with advanced (stage IIIB/IV) NSCLC were reviewed in a single institution (Institut Gustave Roussy).

Vemurafenib in pediatric patients with BRAFV600E mutated high-grade gliomas.

We present three pediatric patients with BRAFV600E mutant high-grade gliomas treated by vemurafenib on a nominative authorization level at our institution. One patient with anaplastic ganglioglioma experienced confirmed partial tumor response and significant clinical improvement and she is alive 20 months after start of treatment. A second patient with ganglioglioma responded transiently to re-introduction of vemurafenib after immunotherapy.

Integrated molecular portrait of non-small cell lung cancers.

Background: Non-small cell lung cancer (NSCLC), a leading cause of cancer deaths, represents a heterogeneous group of neoplasms, mostly comprising squamous cell carcinoma (SCC), adenocarcinoma (AC) and large-cell carcinoma (LCC). The objectives of this study were to utilize integrated genomic data including copy-number alteration, mRNA, microRNA expression and candidate-gene full sequencing data to characterize the molecular distinctions between AC and SCC.

Methods: Comparative genomic hybridization followed by mutational analysis, gene expression and miRNA microarray profiling were performed on 123 paired tumor and non-tumor tissue samples from patients with NSCLC.