南极洲■《自然》一周论文导读丨人类细胞体节时钟的体外特征( 四 ) |白垩纪|地质|土伦|

前列腺癌是全球第二常见的男性癌症。在过去10年中，大规模的综合基因组学研究通过描述成千上万病人的遗传和表观遗传特征，增强了人们对该病的认识。然而，这些研究中描述的大多数肿瘤是从西方人群中获得的。
这里，研究人员通过对2554例前列腺肿瘤的系统比较，绘制了亚洲人群前列腺癌基因图谱，研究表明中国患者的基因组突变特征与西方患者明显不同。
研究人员分析了来自中国原发性前列腺癌患者的208份肿瘤组织样品和匹配的健康对照组织的全基因组、转录组和DNA甲基化数据。结果发现，中国患者的基因组改变特征与西方人群明显不同：41%的肿瘤包含FOXA1突变， 18%的ZNF292和CHD1缺失。研究人员表示，基因组和表观基因组的变化是相关的，并且可以预测疾病的表型和进展。
该研究揭示了东西方人前列腺癌基因组图谱的巨大差异，发现了与前列腺癌预后及生存相关的新基因，将为前列腺癌的治疗、诊断和预后检测提供新的基础。
▲ Abstract
【南极洲■《自然》一周论文导读丨人类细胞体节时钟的体外特征】Prostate cancer is the second most common cancer in men worldwide. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.
In vitro characterization of the human segmentation clock
人类细胞体节时钟的体外特征
▲ 作者：Margarete Diaz-Cuadros、Daniel E. Wagner、Olivier Pourquié ， et al.
▲ 链接：
https://www.nature.com/articles/s41586-019-1885-9
▲ 摘要
在胚胎发生的早期，一种细胞时钟的每一次“滴答”都会促进体节的形成，所产生的体节最终变成了脊椎骨。但一直以来人们尚未证实这种分节时钟是否存在于人类中。但对严重脊柱分节缺陷患者的遗传分析表明，与小鼠分节时钟相关的循环基因在人类中有多个同源基因。
这里，研究人员建立了一个系统，逐个细胞查看时钟基因的动态。结果显示，体外产生的人类前体节中胚层（PSM）细胞重现了分节时钟的振荡。人PSM细胞的振荡周期是小鼠细胞的两倍（5小时与2.5小时），但同样受到FGF、WNT、Notch和YAP信号的调节。研究人员还证明了FGF信号控制振荡的相位和周期。
该研究发现的人类分节时钟代表了理解人类发育生物学的重要里程碑。