A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes.

Background: As panel testing becomes more common in clinical practice, it is important to understand the prevalence and trends associated with the pathogenic variants (PVs) identified. This is especially true for genetically heterogeneous cancers, such as breast cancer (BC), in which PVs in different genes may be associated with various risks and cancer subtypes. The authors evaluated the outcomes of genetic testing among women who had a personal history of BC.

Assessment of in silico protein sequence analysis in the clinical classification of variants in cancer risk genes.

Missense variants represent a significant proportion of variants identified in clinical genetic testing. In the absence of strong clinical or functional evidence, the American College of Medical Genetics recommends that these findings be classified as variants of uncertain significance (VUS). VUSs may be reclassified to better inform patient care when new evidence is available.

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi.

Background: Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions.

Methods: A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory.

Lynch Syndrome Patients with Limited Family History Identified in a Laboratory Setting: A Descriptive Study.

Objective: Patients diagnosed with colorectal cancer before the age of 50 years are recommended for Lynch syndrome (LS) testing according to current clinical guidelines. However, many patients are not identified because of the stringent guidelines on existing diagnostic criteria. The aim of this analysis was to evaluate the ability of existing criteria to adequately ascertain patients appropriate for LS genetic testing.

Phosphatidylglycerol Flip-Flop Suppression due to Headgroup Charge Repulsion.

The kinetics and thermodynamics of 1,2-distearoyl-sn-glycero-3-[phospho(1'-rac-glycerol)] (DSPG) flip-flop in 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) membranes were examined by sum-frequency vibrational spectroscopy (SFVS). The effect of DSPG concentration in the membrane and the influence of electrolyte concentration were examined in an attempt to decipher the role the anionic PG headgroup plays in dictating the dynamics of PG flip-flop for this biologically important lipid species. DSPG flip-flop dynamics and the activation barrier to exchange were found to be directly dependent on the amount of DSPG present in the bilayer.

Analytical validation of a proliferation-based molecular signature used as a prognostic marker in early stage lung adenocarcinoma.

Aims: The aim of these studies was to validate the analytical performance of a cell cycle progression (CCP) gene signature that provides prognostic information for early stage lung adenocarcinomas.

Materials & Methods: Formalin-fixed paraffin-embedded (FFPE) lung resections were evaluated by quantitative RT-PCR for the expression of 31 target and 15 housekeeper genes comprising the CCP score.

Results: The signature had a standard deviation (SD) of 0.

Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579).

The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer (TNBC), and to explore biomarkers based on DNA and protein expression profiles as predictors of response. Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days, and eribulin 1.4 mg/m(2) day 1 and day 8 every 21 days for four cycles.

Lipid flip-flop in binary membranes composed of phosphatidylserine and phosphatidylcholine.

The kinetics and thermodynamics of lipid flip-flop in bilayers composed of 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) were studied using sum-frequency vibrational spectroscopy. The kinetics of DSPC and DPPS flip-flop were examined as a function of temperature and bilayer composition. The rate of DSPC flip-flop did not exhibit any significant dependence on bilayer composition while the rate of DPPS flip-flop was inversely dependent on the mole fraction of DPPS.

The effect of cholesterol on the intrinsic rate of lipid flip-flop as measured by sum-frequency vibrational spectroscopy.

Cholesterol is a major constituent of biological membranes in mammalian cells. Experiments have shown that cholesterol influences the physical properties of the plasma membrane, such as lateral diffusion and phase equilibrium. In addition to controlling the 2-dimensional phase behaviour and mobility of lipids in membranes, cholesterol has also been implicated in the transbilayer diffusion of lipids across the bilayer.

Electrostatic induction of lipid asymmetry.

The asymmetric arrangement of phospholipids between the two leaflets of the plasma membrane of eukaryotic cells is an integral part of cellular function. ATP-dependent translocases capable of selective lipid transport across the membrane are believed to play a role in this lipid asymmetry, but our understanding of this process is incomplete. Here we show the first direct and quantitative experiments demonstrating the induction of phosphatidylserine asymmetry in a membrane by electrostatic association of poly-l-lysine in an attempt to elucidate the complex factors which govern the establishment and maintenance of lipid compositional asymmetry in the plasma membrane on a fundamental level.

Phospholipid flip-flop modulated by transmembrane peptides WALP and melittin.

Select transmembrane proteins found in biogenic membranes are known to facilitate rapid bidirectional flip-flop of lipids between the membrane leaflets, while others have no little or no effect. The particular characteristics which determine the extent to which a protein will facilitate flip-flop are still unknown. To determine if the relative polarity of the transmembrane protein segment influences its capacity for facilitation of flip-flop, we have studied lipid flip-flop dynamics for bilayers containing the peptides WALP(23) and melittin.

Bis(di-2-pyridylmethane-diol-κN,O,N')copper(II) bis-(tetra-fluorido-borate) dihydrate.

The title complex, [Cu(C(11)H(10)N(2)O(2))(2)](BF(4))(2)·2H(2)O, was isolated as a dihydrate from a 1:2 molar mixture of copper(II) tetra-fluoridoborate hexa-hydrate with di-2-pyridyl ketone in aqueous solution. The centrosymmetric complex cation is structurally similar to that found in previously reported salts and exhibits Cu-O bonds deviating by 25 degrees from an octa-hedral geometry by the so-called 'off-axis angle' distortion. The BF(4) (-) anion exhibits a two site disorder of the fluorine atoms [ratio 0.