Abstract：
:Two recurrent mutations, K27M and G34R/V, within histone variant H3.3 were recently identified in ∼50% of pHGGs. Both mutations define clinically and biologically distinct subgroups of pHGGs. Here, we provide further insight about the dominant-negative effect of K27M mutant H3.3, leading to a global reduction of the repressive histone mark H3K27me3. We demonstrate that this is caused by aberrant recruitment of the PRC2 complex to K27M mutant H3.3 and enzymatic inhibition of the H3K27me3-establishing methyltransferase EZH2. By performing chromatin immunoprecipitation followed by next-generation sequencing and whole-genome bisulfite sequencing in primary pHGGs, we show that reduced H3K27me3 levels and DNA hypomethylation act in concert to activate gene expression in K27M mutant pHGGs.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Bender S,Tang Y,Lindroth AM,Hovestadt V,Jones DT,Kool M,Zapatka M,Northcott PA,Sturm D,Wang W,Radlwimmer B,Højfeldt JW,Truffaux N,Castel D,Schubert S,Ryzhova M,Seker-Cin H,Gronych J,Johann PD,Stark S,Meyer J,Mildoi
10.1016/j.ccr.2013.10.006subject
Has Abstractpub_date
2013-11-11 00:00:00pages
660-72issue
5eissn
1535-6108issn
1878-3686pii
S1535-6108(13)00455-8journal_volume
24pub_type
杂志文章相关文献
CANCER CELL文献大全abstract：:Therapies that target estrogen signaling have transformed the treatment of breast cancer. However, the effectiveness of these agents is limited by the development of resistance. Here, an RNAi screen was used to identify modifiers of tamoxifen sensitivity. We demonstrate that CDK10 is an important determinant of resist...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccr.2008.01.001
更新日期：2008-02-01 00:00:00
abstract：:Obesity increases hepatocellular carcinoma (HCC) risks via unknown mediators. We report that hepatic unconventional prefoldin RPB5 interactor (URI) couples nutrient surpluses to inflammation and non-alcoholic steatohepatitis (NASH), a common cause of HCC. URI-induced DNA damage in hepatocytes triggers inflammation via...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccell.2016.05.020
更新日期：2016-07-11 00:00:00
abstract：:The telomere-stabilizing enzyme telomerase is induced in tumors and functionally associated with unlimited replicative potential. To further explore its necessity, transgenic mice expressing SV40 or HPV16 oncogenes, which elicit carcinomas in pancreas and skin, respectively, were rendered telomerase-deficient. Absence...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccr.2004.08.032
更新日期：2004-10-01 00:00:00
abstract：:Acute promyelocytic leukemia (APL) is caused by chromosomal translocations that involve the retinoic acid receptor alpha (RAR) and several other genes to yield X-RAR fusion proteins. Unlike wild-type RARs, which require heterodimerization with the retinoid X receptor (RXR) for their function as DNA-binding transcripti...
journal_title：Cancer cell
pub_type： 评论,杂志文章,评审
doi：10.1016/j.ccr.2007.06.012
更新日期：2007-07-01 00:00:00
abstract：:Adaptive resistance to PI3K-mTOR inhibitors potentially limits the clinical antitumor activities of these agents. In this issue of Cancer Cell, Britschgi and coworkers show that certain tumors acquire resistance to PI3K-mTOR inhibitors through activation of a JAK2-dependent pathway, leading to interleukin-8 secretion....
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/j.ccr.2012.11.012
更新日期：2012-12-11 00:00:00
abstract：:The childhood brain tumor, medulloblastoma, includes four subtypes with very different prognoses. Here, we show that paracrine signals driven by mutant β-catenin in WNT-medulloblastoma, an essentially curable form of the disease, induce an aberrant fenestrated vasculature that permits the accumulation of high levels o...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccell.2016.03.002
更新日期：2016-04-11 00:00:00
abstract：:Controversy over the role of antioxidants in cancer has persisted for decades. Here, we demonstrate that synthesis of the antioxidant glutathione (GSH), driven by GCLM, is required for cancer initiation. Genetic loss of Gclm prevents a tumor's ability to drive malignant transformation. Intriguingly, these findings can...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccell.2014.11.019
更新日期：2015-02-09 00:00:00
abstract：:Van den Eynde et al. publish in this issue of Cancer Cell that metastatic colorectal cancer shows marked heterogeneity in T cell infiltration among different lesions and patients. Measurements of T cell infiltration in metastases by immunoscore offer some prognostic information and support immune editing by coevolving...
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/j.ccell.2018.11.012
更新日期：2018-12-10 00:00:00
abstract：:Ras proteins play a major role in human cancers but have not yielded to therapeutic attack. Ras-driven cancers are among the most difficult to treat and often excluded from therapies. The Ras proteins have been termed "undruggable," based on failures from an era in which understanding of signaling transduction, feedba...
journal_title：Cancer cell
pub_type： 杂志文章,评审
doi：10.1016/j.ccr.2014.02.017
更新日期：2014-03-17 00:00:00
abstract：:Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method ...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccell.2016.06.022
更新日期：2016-08-08 00:00:00
abstract：:Glioma-initiating cells (GICs) are responsible for the initiation and recurrence of gliomas. Here, we identify a molecular mechanism that regulates the self-renewal capacity of patient-derived GICs. We show that TGF-beta and LIF induce the self-renewal capacity and prevent the differentiation of GICs. TGF-beta induces...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccr.2009.02.011
更新日期：2009-04-07 00:00:00
abstract：:Advanced stage papillary serous tumors of the ovary are responsible for the majority of ovarian cancer deaths, yet the molecular determinants modulating patient survival are poorly characterized. Here, we identify and validate a prognostic gene expression signature correlating with survival in a series of microdissect...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccr.2009.10.018
更新日期：2009-12-08 00:00:00
abstract：:In this issue of Cancer Cell, demonstrate a novel mechanism for the oncogenic activity of MLL chimeric proteins. By providing coiled-coil or other dimerization domains, the cytoplasmic partners of MLL fusion proteins donate a platform for MLL homodimerization, allowing recruitment of accessory factors needed to activa...
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/s1535-6108(03)00192-2
更新日期：2003-08-01 00:00:00
abstract：:Adaptive chemoresistance and consequent tumor recurrence present major obstacles to the improvement of the prognosis and quality-of-life of patients with advanced-stage ovarian cancer. In this issue of Cancer Cell, Yu and colleagues describe the critical role of spleen tyrosine kinase (SYK) in paclitaxel resistance by...
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/j.ccell.2015.06.008
更新日期：2015-07-13 00:00:00
abstract：:DNA microarrays make possible the rapid and comprehensive assessment of the transcriptional activity of a cell, and as such have proven valuable in assessing the molecular contributors to biological processes and in the classification of human cancers. The major challenge in using this technology is the analysis of it...
journal_title：Cancer cell
pub_type： 杂志文章,评审
doi：10.1016/s1535-6108(02)00181-2
更新日期：2002-11-01 00:00:00
abstract：:Chromosome rearrangements in B lymphocytes can be initiated by AID-associated double strand breaks (DSBs), with others arising by unclear mechanisms. A recent study by Barlow and colleagues in Cell reports on genomic regions, termed early replicating fragile sites, that may explain many AID-independent DSBs and create...
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/j.ccr.2013.01.017
更新日期：2013-02-11 00:00:00
abstract：:Inhibition of ERK-MAPK signaling by expression of dominant-negative MEK1 in the tumor vasculature suppresses angiogenesis and tumor growth. In an organotypic tissue culture angiogenesis assay, ERK-MAPK inhibition during the migratory phase results in loss of bipolarity, detachment, and cell death of isolated endotheli...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccr.2005.12.021
更新日期：2006-01-01 00:00:00
abstract：:Gene alterations play a prominent role in driving cancer initiation and progression. However, the genetic events that occur in normal cells prior to tumorigenesis are still unknown. Recent studies have started to map somatic mutations in normal human tissues, and here we discuss their implications for our understandin...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccell.2020.11.002
更新日期：2020-11-17 00:00:00
abstract：:Human T cell leukemias can arise from oncogenes activated by specific chromosomal translocations involving the T cell receptor genes. Here we show that five different T cell oncogenes (HOX11, TAL1, LYL1, LMO1, and LMO2) are often aberrantly expressed in the absence of chromosomal abnormalities. Using oligonucleotide m...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/s1535-6108(02)00018-1
更新日期：2002-02-01 00:00:00
abstract：:Adoptively transferred T cells can reject large established tumors, but recurrence due to escape variants frequently occurs. In this issue of Cancer Cell, Engels et al. demonstrate that the affinity of the target peptide to the MHC molecule determines whether large tumors will relapse following adoptive T cell therapy...
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/j.ccr.2013.04.004
更新日期：2013-04-15 00:00:00
abstract：:We identified dynein light chain 1 (DLC1) as a physiologic substrate of p21-activated kinase 1 (Pak1). Pak1-DLC1 interaction plays an essential role in cell survival, which depends on Pak1's phosphorylation of DLC1 on Ser88. Pak1 associates with the complex of DLC1 and BimL, a proapoptotic BH3-only protein, and phosph...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccr.2004.05.022
更新日期：2004-06-01 00:00:00
abstract：:Long non-coding RNAs (lncRNAs) are critical for regulating HOX genes, aberration of which is a dominant mechanism for leukemic transformation. How HOX gene-associated lncRNAs regulate hematopoietic stem cell (HSC) function and contribute to leukemogenesis remains elusive. We found that HOTTIP is aberrantly activated i...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccell.2019.10.011
更新日期：2019-12-09 00:00:00
abstract：:Recent evidence suggests that human cells require more genetic changes for neoplastic transformation than do their murine counterparts. However, a precise enumeration of these differences has never been undertaken. We have determined that perturbation of two signaling pathways-involving p53 and Raf-suffices for the tu...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccr.2004.07.009
更新日期：2004-08-01 00:00:00
abstract：:Women with ErbB2-positive breast cancer have a poor prognosis, and frequently, chemotherapy treatment is ineffective. The ErbB2-targeted antibody trastuzumab improves survival when given with chemotherapy to patients with ErbB2-overexpressing metastatic disease, but treatment is not curative, and primary resistance is...
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/j.ccr.2004.08.001
更新日期：2004-08-01 00:00:00
abstract：:The involvement of the homologous to E6-AP carboxyl terminus (HECT)-type E3s in crucial signaling pathways implicated in tumorigenesis is presently an area of intense research and extensive scientific interest. This review highlights recent discoveries on the ubiquitin-mediated degradation of crucial tumor suppressor ...
journal_title：Cancer cell
pub_type： 杂志文章,评审
doi：10.1016/j.ccr.2008.06.001
更新日期：2008-07-08 00:00:00
abstract：:Genome-wide cancer mutation analyses are revealing an extensive landscape of functional mutations within the noncoding genome, with profound effects on the expression of long noncoding RNAs (lncRNAs). While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, we now underst...
journal_title：Cancer cell
pub_type： 杂志文章,评审
doi：10.1016/j.ccell.2016.03.010
更新日期：2016-04-11 00:00:00
abstract：:The erythroleukemia developed by spi-1/PU.1 transgenic mice is a multistage process characterized by an early arrest of the proerythroblast differentiation followed later on by malignant transformation. Herein, we report the presence of acquired mutations in the SCF receptor gene (Kit) in 86% of tumors isolated during...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccr.2005.11.009
更新日期：2005-12-01 00:00:00
abstract：:Mutant RAS-driven tumorigenesis was thought for decades to arise independently of wild-type RAS isoforms, but recent evidence indicates wild-type isoforms are involved. In this issue of Cancer Cell, Grabocka and colleagues report how the loss of wild-type RAS alters oncogenic signaling and dampens the DNA-damage respo...
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/j.ccr.2014.01.029
更新日期：2014-02-10 00:00:00
abstract：:Although signaling from phosphatidylinositol 3-kinase (PI3K) and AKT to mechanistic target of rapamycin (mTOR) is prominently dysregulated in high-grade glial brain tumors, blockade of PI3K or AKT minimally affects downstream mTOR activity in glioma. Allosteric mTOR inhibitors, such as rapamycin, incompletely block mT...
journal_title：Cancer cell
pub_type： 杂志文章
doi：10.1016/j.ccell.2017.01.014
更新日期：2017-03-13 00:00:00
abstract：:The mechanisms through which tumor antigen-specific T cells are elicited in natural or chemotherapy-induced immunosurveillance have been elusive. In this issue of Cancer Cell, two papers by Broz and colleagues and Ruffell and colleagues delineate an important role for a specific dendritic cell subset characterized by ...
journal_title：Cancer cell
pub_type： 评论,杂志文章
doi：10.1016/j.ccell.2014.10.008
更新日期：2014-11-10 00:00:00
