一周快讯：本周表观文献精选（2018.1.7）

中科大瞿昆教授研究组首次揭示T细胞淋巴瘤的表观遗传调控机制

Chromatin Accessibility Landscape of Cutaneous T Cell Lymphoma and Dynamic Response to HDAC Inhibitors

Kun Qu,Lisa C.Zaba , Ansuman T. Satpathy, Paul G. Giresi,Rui Li, Yonghao Jin, Nathalie Schmitt, Ziba Rahbar, Hideki Ueno, William J. Greenleaf, Youn H. Kim, Howard Y. Chang.

原文链接：

http://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30204-0

原文摘要：

Here, we define the landscape and dynamics of active regulatory DNA in cutaneous T cell lymphoma (CTCL) by ATAC-seq. Analysis of 111 human CTCL and control samples revealed extensive chromatin signatures that distinguished leukemic, host, and normal CD4+ T cells. We identify three dominant patterns of transcription factor (TF) activation that drive leukemia regulomes, as well as TF deactivations that alter host T cells in CTCL patients. Clinical response to histone deacetylase inhibitors (HDACi) is strongly associated with a concurrent gain in chromatin accessibility. HDACi causes distinct chromatin responses in leukemic and host CD4+ T cells, reprogramming host T cells toward normalcy. These results provide a foundational framework to study personal regulomes in human cancer and epigenetic therapy.

荷兰学者发表肿瘤液态活检新方法

Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

Myron G. Best, Nik Sol, Sjors G.J.G. In‘t Veld, Adrienne Vancura, Mirte Muller, Anna-Larissa N.Niemeijer, Aniko V. Fejes, Lee-Ann Tjon Kon Fat, Anna E. Huis In‘t Veld, Cyra Leurs, Tessa Y. Le Large, Laura L. Meijer, Irsan E. Kooi, François Rustenburg, Pepijn Schellen, Heleen Verschueren, Edward Post, Laurine E. Wedekind, Jillian Bracht, Michelle Esenkbrink, Leon Wils, Francesca Favaro, Jilian D.Schoonhoven, Jihane Tannous, Hanne Meijers-Heijboer, Geert Kazemier, Elisa Giovannetti, Jaap C.Reijneveld, Sander Idema, Joep Killestein, Michal Heger, Saskia C. de Jager, Rolf T. Urbanus, Imo E.Hoefer, Gerard Pasterkamp, Christine Mannhalter, Jose Gomez-Arroyo, Harm-Jan Bogaard, David P.Noske, W. Peter Vandertop, Daan van den Broek, Bauke Ylstra, R. Jonas A. Nilsson, Pieter Wesseling, Niki Karachaliou, Rafael Rosell, Elizabeth Lee-Lewandrowski, Kent B. Lewandrowski, Bakhos A. Tannous, Adrianus J. de Langen, Egbert F. Smit, Michel M. van den Heuvel. Thomas Wurdinger.

原文链接 ：

http://www.cell.com/cancer-cell/abstract/S1535-6108(17)30296-9

原文摘要：

Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selecion of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92–0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83–0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selecion of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.

癌症究竟是遗传性的还是常常认为的由环境所致的

Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention

Cristian Tomasett，  Lu Li ,  Bert Vogelstein

原文链接 ：

http://science.sciencemag.org/content/355/6331/1330

原文摘要：

Cancers are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replication errors (R). We studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries throughout the world. The data revealed a strong correlation (median = 0.80) between cancer incidence and normal stem cell divisions in all countries, regardless of their environment. The major role of R mutations in cancer etiology was supported by an independent approach, based solely on cancer genome sequencing and epidemiological data, which suggested that R mutations are responsible for two-thirds of the mutations in human cancers. All of these results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment. Moreover, they accentuate the importance of early detection and intervention to reduce deaths from the many cancers arising from unavoidable R mutations.

表观遗传学揭示恶性儿童白血病患者的差异

Genome-wide DNA methylation is predictive of outcome in juvenile myelomonocytic leukemia

Elliot Stieglitz，Tail Mazor，Adam B.Olshen，Huimin Geng，Laura C.Gelston，Jon Akutagawa，Daniel B.Lipka，Christoph Plass，Christian Flotho，Farid F.Chehab，Benjamin S.Braun，Joseph F.Costello&Mignon L.Loh

原文链接：

http://www.nature.com/articles/s41467-017-02178-9

原文摘要：

Juvenile myelomonocytic leukemia (JMML) is a myeloproliferative disorder of childhood caused by mutations in the Ras pathway. Outcomes in JMML vary markedly from spontaneous resolution to rapid relapse after hematopoietic stem cell transplantation. Here, we hypothesized that DNA methylation patterns would help predict disease outcome and therefore performed genome-wide DNA methylation profiling in a cohort of 39 patients. Unsupervised hierarchical clustering identifies three clusters of patients. Importantly, these clusters differ significantly in terms of 4-year event-free survival, with the lowest methylation cluster having the highest rates of survival. These findings were validated in an independent cohort of 40 patients. Notably, all but one of 14 patients experiencing spontaneous resolution cluster together and closer to 22 healthy controls than to other JMML cases. Thus, we show that DNA methylation patterns in JMML are predictive of outcome and can identify the patients most likely to experience spontaneous resolution.

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