The cost of restricting corporate takeovers: a lesson from Switzerland

Consolidation and merger of corporations ; Switzerland

A high-risk, Double-Hit, group of newly diagnosed myeloma identified by genomic analysis

Patients with newly diagnosed multiple myeloma (NDMM) with high-risk disease are in need of new treatment strategies to improve the outcomes. Multiple clinical, cytogenetic, or gene expression features have been used to identify high-risk patients, each of which has significant weaknesses. Inclusion of molecular features into risk stratification could resolve the current challenges. In a genome-wide analysis of the largest set of molecular and clinical data established to date from NDMM, as part of the Myeloma Genome Project, we have defined DNA drivers of aggressive clinical behavior. Whole-genome and exome data from 1273 NDMM patients identified genetic factors that contribute significantly to progression free survival (PFS) and overall survival (OS) (cumulative R2 = 18.4% and 25.2%, respectively). Integrating DNA drivers and clinical data into a Cox model using 784 patients with ISS, age, PFS, OS, and genomic data, the model has a cumlative R2 of 34.3% for PFS and 46.5% for OS. A high-risk subgroup was defined by recursive partitioning using either a) bi-allelic TP53 inactivation or b) amplification (≥4 copies) of CKS1B (1q21) on the background of International Staging System III, comprising 6.1% of the population (median PFS = 15.4 months; OS = 20.7 months) that was validated in an independent dataset. Double-Hit patients have a dire prognosis despite modern therapies and should be considered for novel therapeutic approaches

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers

Disentangling the Trichoderma viridescens complex

Trichoderma viridescens is recognised as a species complex. Multigene analyses based on the translation elongation factor 1-alpha encoding gene (tef1), a part of the rpb2 gene, encoding the second largest RNA polymerase subunit and the larger subunit of ATP citrate lyase (acl1) reveals 13 phylogenetic species with little or no phenotypic differentiation. This is the first use of acl1 in Trichoderma phylogenetics. The typification of T. viridescens s.str. is clarified and Hypocrea viridescens is replaced by the new name T. paraviridescens. Besides these two species, eleven are phylogenetically recognised and T. olivascens, T. viridarium, T. virilente, T. trixiae, T. viridialbum, T. appalachiense, T. neosinense, T. composticola, T. nothescens and T. sempervirentis are formally described and illustrated. Several species produce yellow diffusing pigment on cornmeal dextrose agar, particularly after storage at 15 °C, while T. olivascens is characterised by the formation of an olivaceous pigment. The results are compared with earlier publications on this group of species

Pretoriana, no. 054, Aug. 1967

Die lotgevalle van die Staatsmodelschoolgebou, 1902-1910 / Jan Ploeger -- One thousand meetings around Pretoria's "Horseshoe" / H.P.H. Behrens -- Danville : westelike voorstad van Pretoria / G.J. van Eck -- Besonderhede aangaande Regter S.G. Jorissen / Jan Ploeger -- Grondwet van Genootskap Oud-Pretori

Pretoriana, no. 055 Dec. 1967

Dr. T.S. van Rooyen -- Die straatname van die Pretoriase voorstad Danville-uitbreiding no. 2 / G.J. van Eck -- Lys van besienswaardighede in Pretoria / H.M. Rex -- Skooltuinekompetisie 1967 -- Jaarverslag van die Genootskap Oud-Pretoria / N.A. Coetzee -- Lotgevalle van die Staatsmodelskoolgebou, 1909-1931 / J. Ploeger -- Old Pretoria Society constitutio