betway亚洲QIMRBERCHOFER医学研究所

抽象性 :跨基因组共研究精神分裂症(479例2 937控件)并用P < 10(5)测试12项跟踪中,3项有强独立支持(P < 5x10(4)),整体复制模式不太可能偶然实现(P=9x10(8))。元分析为ZNF804A关联提供最强证据(P=1.61x10-7),当受到影响的pheno类型包括双极失序时加强这一点(P=9.96x10-9)。

抽象性 :Breast cancer is the most common cancer among women Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC) The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)) Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility

抽象性 :必威体育BW跨基因组关联研究旨在发现与复杂特征相联的SNP测试单个SNP避免假正数时使用严格意义阈值而牺牲增加假负值最近,我们开发量化特征方法 估计变异计算在此我们开发出这个方法 深入案例控制研究线性混合模型分析二元特征并转换估计值为责任尺度,即调整尺度和确定案例样本我们通过理论模拟显示方法不带偏见并显示Crohn疾病、双极失序和I型糖尿病的重负有很大一部分由常用SNP标注

抽象性 :We characterized the mutational landscape of melanoma, the form of skin cancer with the highest mortality rate, by sequencing the exomes of 147 melanomas Sun-exposed melanomas had markedly more ultraviolet (UV)-like C>T somatic mutations compared to sun-shielded acral, mucosal and uveal melanomas Among the newly identified cancer genes was PPP6C, encoding a serine/threonine phosphatase, which harbored mutations that clustered in the active site in 12% of sun-exposed melanomas, exclusively in tumors with mutations in BRAF or NRAS Notably, we identified a recurrent UV-signature, an activating mutation in RAC1 in 92% of sun-exposed melanomas This activating mutation, the third most frequent in our cohort of sun-exposed melanoma after those of BRAF and NRAS, changes Pro29 to serine (RAC1P29S) in the highly conserved switch I domain Crystal structures, and biochemical and functional studies of RAC1P29S showed that the alteration releases the conformational restraint conferred by the conserved proline, causes an increased binding of the protein to downstream effectors, and promotes melanocyte proliferation and migration These findings raise the possibility that pharmacological inhibition of downstream effectors of RAC1 signaling could be of therapeutic benefit

抽象性 :前台显示肿瘤渗透淋巴细胞(TILs)在新诊断出三负乳癌(TNBC)中的预测重要性研究中,我们的目标是验证这些发现并调查Trazumab对HER2超表达性疾病(HER2+)的关联未来反向研究使用Finheraadjivant测试第三阶段样本进行,录入1010名BC初级病人,其中778名HER2非简单化HER2+病(n=232)随机化为9周truzumab或无truzumab除化疗两位病理学家独立量化935(92.6%)可用滑动远端免病生存和与truzumab交互作用初级端点在Cox回归模型中研究结果确认我们前一次发现TNBC中(n=134)每增加10%TIL与TNBC远程复发下降大相联DDFS危险比调整临床病理学因数 : 0.7795%置信区间 0.61-0.98,P=0.02HER2+BC中(n=209),淋巴渗透量每增加10%与随机转入trazumab臂的病人远程复发率下降大相联(DDFS插件=0.025)。诊断时高端TIL与初级TNBC远程复发率下降大相联这些数据证实了我们先前的数据并进一步支持TIL应被视为BC子型中稳健预测因子并首次报告高层次TIL与HER2+疾病的trazumab增益关联betway亚洲深入研究TN和HER2+BCs为何能或不能生成主机抗脉冲响应和Tstruzumab如何优修改免疫微环境