2016年6月30日讯/生物谷BIOON/近日,刊登于国际杂志Nature Communications上的一项研究论文中,来自南安普顿大学和伯恩茅斯皇家医院的研究人员通过研究鉴别出了所有慢性淋巴细胞白血病(CLL)患者很有可能共享的一种特殊基因网络,该研究或为后期开发新型靶向疗法改善患者的生活质量及生存期提供新的思路。
该研究是一项国际联合研究的的一部分,而这项国际联合研究项目旨在检测表观遗传分析在临床诊断和精准医学中的可行性。在所有癌症和其它多种疾病中都会出现表观遗传变异,基于全球多个实验室的技术进展,大量研究都揭示了表观遗传学检测的准确性和稳定性;未来临床研究者们或许会在多种疾病中应用这些方法,而且有预测显示,表观遗传学测试未来或将广泛用于针对癌症及其它疾病选择新型的个体化疗法。
研究人员希望促成全球科学家的努力来对人类肿瘤开展首个“染色质景观”的大规模分析,研究者Strefford说道,我们已经深入分析了CLL患者表观基因组中的变异,同时也鉴别出了疾病特异性的改变,而这对于后期有效区分疾病类型或鉴别合适的疗法或将非常重要,表观遗传学研究可以为我们提供一扇门来帮助改善科学家们对疾病的诊断以及更多针对患者的个体化疗法选择。
在不同患者中慢性淋巴细胞白血病会以不同的比率来发生,而且其中有些患者对疗法反应较好,检测特殊的基因缺陷或可帮助预测患者的预后,很显然还有其它生物性因素也会影响患者的预后;本文研究中研究者揭示了基因的行为以及癌细胞中多个基因的相互作用,他们希望未来可以帮助开发针对不同患者的新型疗法。(基因宝jiyinbao.com)
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Chromatin accessibility maps of chronic lymphocytic leukaemia identify subtype-specific epigenome signatures and transcription regulatory networks
André F. Rendeiro, Christian Schmidl, Jonathan C. Strefford, Renata Walewska, Zadie Davis, Matthias Farlik, David Oscier & Christoph Bock
Chronic lymphocytic leukaemia (CLL) is characterized by substantial clinical heterogeneity, despite relatively few genetic alterations. To provide a basis for studying epigenome deregulation in CLL, here we present genome-wide chromatin accessibility maps for 88 CLL samples from 55 patients measured by the ATAC-seq assay. We also performed ChIPmentation and RNA-seq profiling for ten representative samples. Based on the resulting data set, we devised and applied a bioinformatic method that links chromatin profiles to clinical annotations. Our analysis identified sample-specific variation on top of a shared core of CLL regulatory regions. IGHV mutation status—which distinguishes the two major subtypes of CLL—was accurately predicted by the chromatin profiles and gene regulatory networks inferred for IGHV-mutated versus IGHV-unmutated samples identified characteristic differences between these two disease subtypes. In summary, we discovered widespread heterogeneity in the chromatin landscape of CLL, established a community resource for studying epigenome deregulation in leukaemia and demonstrated the feasibility of large-scale chromatin accessibility mapping in cancer cohorts and clinical research.