The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space.
The DNA methylation landscape of glioblastoma disease progression shows extensive heterogeneity in time and space.
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DOI：
10.1038/s41591-018-0156-x
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发表时间：
2018-10
期刊：
影响因子：
82.9
通讯作者：
Bock C
中科院分区：
文献类型：
--
作者：
Klughammer J;Kiesel B;Roetzer T;Fortelny N;Nemc A;Nenning KH;Furtner J;Sheffield NC;Datlinger P;Peter N;Nowosielski M;Augustin M;Mischkulnig M;Ströbel T;Alpar D;Ergüner B;Senekowitsch M;Moser P;Freyschlag CF;Kerschbaumer J;Thomé C;Grams AE;Stockhammer G;Kitzwoegerer M;Oberndorfer S;Marhold F;Weis S;Trenkler J;Buchroithner J;Pichler J;Haybaeck J;Krassnig S;Mahdy Ali K;von Campe G;Payer F;Sherif C;Preiser J;Hauser T;Winkler PA;Kleindienst W;Würtz F;Brandner-Kokalj T;Stultschnig M;Schweiger S;Dieckmann K;Preusser M;Langs G;Baumann B;Knosp E;Widhalm G;Marosi C;Hainfellner JA;Woehrer A;Bock C
胶质母细胞瘤的特点是广泛的遗传和转录异质性，但对表观基因组在胶质母细胞瘤疾病进展中的作用知之甚少。在这里，我们展示了匹配的原发和复发胶质母细胞瘤的DNA甲基化的基因组图，使用了通过国家患者登记选择的高度注释的临床队列的数据。我们证明了在大量常规收集的福尔马林固定石蜡包埋(FFPE)样本中绘制DNA甲基化图谱的可行性，并验证了亚硫酸氢盐测序是一种多用途的分析方法，允许我们推断一系列不同的基因、表观遗传和转录特征的侧写肿瘤样本。基于这些数据，我们确定了原发和复发肿瘤之间的细微差异，DNA甲基化和肿瘤微环境之间的联系，以及表观遗传肿瘤异质性与患者生存的关系。总之，这项研究建立了一个开放的资源，用于解剖遗传多样性和异质性癌症中的DNA甲基化异质性，并论证了将表观基因组学、放射学和数字病理学整合为国家队列的可行性，从而利用作为常规临床实践的一部分收集的现有样本和数据。
Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little is known about the role of the epigenome in glioblastoma disease progression. Here, we present genome-scale maps of DNA methylation in matched primary and recurring glioblastoma tumors, using data from a highly annotated clinical cohort that was selected through a national patient registry.. We demonstrate the feasibility of DNA methylation mapping in a large set of routinely collected formalin-fixed paraffin-embedded (FFPE) samples, and we validate bisulfite sequencing as a multi-purpose assay that allowed us to infer a range of different genetic, epigenetic, and transcriptional characteristics of the profiled tumor samples. Based on these data, we identified subtle differences between primary and recurring tumors, links between DNA methylation and the tumor microenvironment, and an association of epigenetic tumor heterogeneity with patient survival. In summary, this study establishes an open resource for dissecting DNA methylation heterogeneity in a genetically diverse and heterogeneous cancer, and it demonstrates the feasibility of integrating epigenomics, radiology, and digital pathology for a national cohort, thereby leveraging existing samples and data collected as part of routine clinical practice.
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影响因子：
64.8
作者：
Capper D;Jones DTW;Sill M;Hovestadt V;Schrimpf D;Sturm D;Koelsche C;Sahm F;Chavez L;Reuss DE;Kratz A;Wefers AK;Huang K;Pajtler KW;Schweizer L;Stichel D;Olar A;Engel NW;Lindenberg K;Harter PN;Braczynski AK;Plate KH;Dohmen H;Garvalov BK;Coras R;Hölsken A;Hewer E;Bewerunge-Hudler M;Schick M;Fischer R;Beschorner R;Schittenhelm J;Staszewski O;Wani K;Varlet P;Pages M;Temming P;Lohmann D;Selt F;Witt H;Milde T;Witt O;Aronica E;Giangaspero F;Rushing E;Scheurlen W;Geisenberger C;Rodriguez FJ;Becker A;Preusser M;Haberler C;Bjerkvig R;Cryan J;Farrell M;Deckert M;Hench J;Frank S;Serrano J;Kannan K;Tsirigos A;Brück W;Hofer S;Brehmer S;Seiz-Rosenhagen M;Hänggi D;Hans V;Rozsnoki S;Hansford JR;Kohlhof P;Kristensen BW;Lechner M;Lopes B;Mawrin C;Ketter R;Kulozik A;Khatib Z;Heppner F;Koch A;Jouvet A;Keohane C;Mühleisen H;Mueller W;Pohl U;Prinz M;Benner A;Zapatka M;Gottardo NG;Driever PH;Kramm CM;Müller HL;Rutkowski S;von Hoff K;Frühwald MC;Gnekow A;Fleischhack G;Tippelt S;Calaminus G;Monoranu CM;Perry A;Jones C;Jacques TS;Radlwimmer B;Gessi M;Pietsch T;Schramm J;Schackert G;Westphal M;Reifenberger G;Wesseling P;Weller M;Collins VP;Blümcke I;Bendszus M;Debus J;Huang A;Jabado N;Northcott PA;Paulus W;Gajjar A;Robinson GW;Taylor MD;Jaunmuktane Z;Ryzhova M;Platten M;Unterberg A;Wick W;Karajannis MA;Mittelbronn M;Acker T;Hartmann C;Aldape K;Schüller U;Buslei R;Lichter P;Kool M;Herold-Mende C;Ellison DW;Hasselblatt M;Snuderl M;Brandner S;Korshunov A;von Deimling A;Pfister SM
通讯作者：
Pfister SM
食管鳞状细胞癌的空间瘤内异质性和时间克隆进化
影响因子：
30.8
作者：
Hao, Jia-Jie;Lin, De-Chen;Dinh, Huy Q.;Mayakonda, Anand;Jiang, Yan-Yi;Chang, Chen;Jiang, Ye;Lu, Chen-Chen;Shi, Zhi-Zhou;Xu, Xin;Zhang, Yu;Cai, Yan;Wang, Jin-Wu;Zhan, Qi-Min;Wei, Wen-Qiang;Berrnan, Benjamin P.;Wang, Ming-Rong;Koeffler, H. Phillip
通讯作者：
Koeffler, H. Phillip
影响因子：
1.1
作者：
Bienkowski, Michal;Berghoff, Anna S.;Preusser, Matthias
通讯作者：
Preusser, Matthias
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
50.3
作者：
Kim, Jinkuk;Lee, In-Hee;Nam, Do-Hyun
通讯作者：
Nam, Do-Hyun