Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

遺伝性乳癌の遺伝学的・臨床学的特徴を解明 --BRCA1/2 変異乳癌は両アレルの不活化の有無により異なった特徴を持つ--. 京都大学プレスリリース. 2020-10-26.The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1, 995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

Combined effects of plant competition and insect herbivory hinder invasiveness of an introduced thistle

The biotic resistance hypothesis is a dominant paradigm for why some introduced species fail to become invasive in novel environments. However, predictions of this hypothesis require further empirical field tests. Here, we focus on evaluating two biotic factors known to severely limit plants, interspecific com­petition and insect herbivory, as mechanisms of biotic resis­tance. We experimentally evaluated the independent and com­bined effects of three levels of competition by tallgrass prairie vegetation and two levels of herbivory by native insects on seedling regeneration, size, and subsequent flowering of the Eurasian Cirsium vulgare, a known invasive species elsewhere, and compared its responses to those of the ecologically sim­ilar and co-occurring native congener C. altissimum. Seedling emergence of C. vulgare was greater than that of C. altissimum, and that emergence was reduced by the highest level of in­terspecific competition. Insect leaf herbivory was also greater on C. vulgare than on C. altissimum at all levels of competition. Herbivory on seedlings dramatically decreased the proportion of C. vulgare producing flower heads at all competition levels, but especially at the high competition level. Competition and herbivory interacted to significantly decrease plant survival and biomass, especially for C. vulgare. Thus, both competition and herbivory limited regeneration of both thistles, but their effects on seedling emergence, survival, size and subsequent reproduction were greater for C. vulgare than for C. altissimum. These results help explain the unexpectedly low abundance recorded for C. vulgare in western tallgrass prairie, and also provide strong support for the biotic resistance hypothesis

No interaction between competition and herbivory in limiting introduced Cirsium vulgare rosette growth and reproduction

Both competition and herbivory have been shown to reduce plant survival, growth, and reproduction. Much less is known about whether competition and herbivory interact in determining plant performance, especially for introduced, weedy plant species in the invaded habitat. We simultaneously evaluated both the main and interactive effects of plant neighbors and insect herbivory on rosette growth and seed reproduction in the year of flowering for Cirsium vulgare (bull thistle, spear thistle), an introduced Eurasian species, in tallgrass prairie in 2 years. Effects of insect herbivory were strong and consistent in both years, causing reduced plant growth and seed production, whereas the effects of competition with established vegetation were weak. The amount of herbivore damage inflicted on rosettes did not depend on the presence of neighbor plants. We also found no interaction between competition and herbivory on key parameters of plant growth and fitness. The results of this study contradict the hypothesis that competitive context interacts with insect herbivory in limiting the invasiveness of this introduced thistle. Further, the results provide additional, experimental evidence that high levels of herbivory on established rosettes by native insects exert significant biotic resistance to the invasiveness of C. vulgare in western tallgrass prairie

Magnetic Properties of Fibonacci-Modulated Fe-Au Multilayer Metamaterials

Herein we experimentally study magnetic multilayer metamaterials with broken translational symmetry. Epitaxially-grown iron-gold (Fe-Au) multilayers modulated using Fibonacci sequence—referred to as magnetic inverse Fibonacci-modulated multilayers (IFMs)—are prepared using ultra-high-vacuum vapor deposition. Experimental results of in-situ reflection high-energy electron diffraction, magnetization curves, and ferromagnetic resonance demonstrate that the epitaxially-grown Fe-Au IFMs have quasi-isotropic magnetization, in contrast to the in-plane magnetization easy axis in the periodic multilayers

Supplement 1. Data files and R-scripts for statistical analysis and integral projection modeling described in the main text.

<h2>File List</h2><div> <p><a href="Establishment.and.survival.csv">Establishment.and.survival.csv</a> (MD5: a2d7c17a4976be7762b43a815126fdbe)</p> <p><a href="Reproduction 2006&2007.csv">Reproduction 2006&2007.csv</a> (MD5: 54ce76bd982cb1e15162c40ea7276aed)</p> <p><a href="July 2007 census and biomass2 edited.csv">July 2007 census and biomass2 edited.csv</a> (MD5: 38a41af122fb6b90dfb723b3b740a6e0)</p> <p><a href="Tall Thistle 2006 Updated Dec 2010.csv">Tall Thistle 2006 Updated Dec 2010.csv</a> (MD5: 5dd859826ace0e751cd51c10bc4d4c0f)</p> <p><a href="Tall Thistle 2007 Updated Dec 2010.csv">Tall Thistle 2007 Updated Dec 2010.csv</a> (MD5: 0de9c392b393e594a49c65a3f3118235)</p> <p><a href="IPM statistics bolting.R">IPM statistics bolting.R</a> (MD5: dc8c3868f1e24ad0446c0266a529c361)</p> <p><a href="IPM Statistics growth.R">IPM Statistics growth.R</a> (MD5: 21260c8b65c0606e110207c2060800d9)</p> <p><a href="IPM statistics recruitment.R">IPM statistics recruitment.R</a> (MD5: 6914a0c0c892f76c0977c24a9a649eea)</p> <p><a href="IPM statistics initial size.R">IPM statistics initial size.R</a> (MD5: cff5c4ee3d3c58ff056d3e8aa390f7c1)</p> <p><a href="IPM statistics seed production.R">IPM statistics seed production.R</a> (MD5: 1de9453716f25b3d8f5ae4b276237050)</p> <p><a href="IPM statistics survival.R">IPM statistics survival.R</a> (MD5: 4b93fdf09019f572f0e88715fba0482d)</p> <p><a href="IPM.Parameters.csv">IPM.Parameters.csv</a> (MD5: d3ab447e0c4ddc1ae12d89af3fb5d5d9)</p> <p><a href="IPM model and bootstrap.R">IPM model and bootstrap.R</a> (MD5: 5e92d9d9072b67f4ca9e1e20538f99b9)</p> </div><h2>Description</h2><div> <p>For the statistical analysis the file “IPM statistics growth.R” needs to be executed first. </p> <p>The statistical results are saved in the file “IPM.Parameters.csv”, allowing the execution of the “IPM model and bootstrap.R”-file without running the statistics scripts first.</p> <p>Description of variables:</p> <div> <p><i>Establishment and Survival.csv</i></p> </div> -- TABLE: Please see in attached file. -- <p> </p> <div> <p><i>Reproduction 2006&2007</i></p> </div> -- TABLE: Please see in attached file. -- <p> </p> <div> <p><i>July 2007 census and biomass2 edited</i></p> </div> -- TABLE: Please see in attached file. -- <br> <p> </p> <div> <p><i>Tall thistle 2006 Updated Dec 2010</i></p> <p><i>Tall thistle 2007Updated Dec 2010 </i></p> </div> -- TABLE: Please see in attached file. -- </div