当前位置： SCI文献检索 > NATURE GENETICS期刊下所有文献 > DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia.

DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia.

Abstract：

:Charting differences between tumors and normal tissue is a mainstay of cancer research. However, clonal tumor expansion from complex normal tissue architectures potentially obscures cancer-specific events, including divergent epigenetic patterns. Using whole-genome bisulfite sequencing of normal B cell subsets, we observed broad epigenetic programming of selective transcription factor binding sites coincident with the degree of B cell maturation. By comparing normal B cells to malignant B cells from 268 patients with chronic lymphocytic leukemia (CLL), we showed that tumors derive largely from a continuum of maturation states reflected in normal developmental stages. Epigenetic maturation in CLL was associated with an indolent gene expression pattern and increasingly favorable clinical outcomes. We further uncovered that most previously reported tumor-specific methylation events are normally present in non-malignant B cells. Instead, we identified a potential pathogenic role for transcription factor dysregulation in CLL, where excess programming by EGR and NFAT with reduced EBF and AP-1 programming imbalances the normal B cell epigenetic program.

journal_name

Nat Genet

journal_title

Nature genetics

authors

Oakes CC,Seifert M,Assenov Y,Gu L,Przekopowitz M,Ruppert AS,Wang Q,Imbusch CD,Serva A,Koser SD,Brocks D,Lipka DB,Bogatyrova O,Weichenhan D,Brors B,Rassenti L,Kipps TJ,Mertens D,Zapatka M,Lichter P,Döhner H,Küppe

doi

10.1038/ng.3488

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

253-64

issue

3

eissn

1061-4036

issn

1546-1718

pii

ng.3488

journal_volume

48

pub_type

杂志文章

相关文献

NATURE GENETICS文献大全
  • Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.

    abstract：:Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesting in early childho...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng2013

    authors： Scheper GC,van der Klok T,van Andel RJ,van Berkel CG,Sissler M,Smet J,Muravina TI,Serkov SV,Uziel G,Bugiani M,Schiffmann R,Krägeloh-Mann I,Smeitink JA,Florentz C,Van Coster R,Pronk JC,van der Knaap MS

    更新日期：2007-04-01 00:00:00

  • Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss.

    abstract：:Age-related hearing loss (AHL) in common inbred mouse strains is a genetically complex quantitative trait. We found a synonymous single-nucleotide polymorphism in exon 7 of Cdh23 that shows significant association with AHL and the deafness modifier mdfw (modifer of deafwaddler). The hypomorphic Cdh23(753A) allele caus...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1226

    authors： Noben-Trauth K,Zheng QY,Johnson KR

    更新日期：2003-09-01 00:00:00

  • An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers.

    abstract：:Recent studies indicate that a subclass of APOBEC cytidine deaminases, which convert cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction, may induce mutation clusters in human tumors. We show here that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates wit...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2702

    authors： Roberts SA,Lawrence MS,Klimczak LJ,Grimm SA,Fargo D,Stojanov P,Kiezun A,Kryukov GV,Carter SL,Saksena G,Harris S,Shah RR,Resnick MA,Getz G,Gordenin DA

    更新日期：2013-09-01 00:00:00

  • Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus.

    abstract：:Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethni...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.766

    authors： Adrianto I,Wen F,Templeton A,Wiley G,King JB,Lessard CJ,Bates JS,Hu Y,Kelly JA,Kaufman KM,Guthridge JM,Alarcón-Riquelme ME,BIOLUPUS and GENLES Networks.,Anaya JM,Bae SC,Bang SY,Boackle SA,Brown EE,Petri MA,Gallant C

    更新日期：2011-03-01 00:00:00

  • A murine model of Menkes disease reveals a physiological function of metallothionein.

    abstract：:Human Menkes disease and the murine Mottled phenotype are X-linked diseases that result from copper deficiency due to mutations in a copper-effluxing ATPase, designated ATP7A. Male mice with the Mottled-Brindled allele (Mo-brJ) accumulate copper in the intestine, fail to export copper to peripheral organs and die a fe...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0696-219

    authors： Kelly EJ,Palmiter RD

    更新日期：1996-06-01 00:00:00

  • miRNA regulation of Sdf1 chemokine signaling provides genetic robustness to germ cell migration.

    abstract：:microRNAs (miRNAs) function as genetic rheostats to control gene output. Based on their role as modulators, it has been postulated that miRNAs canalize development and provide genetic robustness. Here, we uncover a previously unidentified regulatory layer of chemokine signaling by miRNAs that confers genetic robustnes...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.758

    authors： Staton AA,Knaut H,Giraldez AJ

    更新日期：2011-03-01 00:00:00

  • Vitamin C modulates TET1 function during somatic cell reprogramming.

    abstract：:Vitamin C, a micronutrient known for its anti-scurvy activity in humans, promotes the generation of induced pluripotent stem cells (iPSCs) through the activity of histone demethylating dioxygenases. TET hydroxylases are also dioxygenases implicated in active DNA demethylation. Here we report that TET1 either positivel...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2807

    authors： Chen J,Guo L,Zhang L,Wu H,Yang J,Liu H,Wang X,Hu X,Gu T,Zhou Z,Liu J,Liu J,Wu H,Mao SQ,Mo K,Li Y,Lai K,Qi J,Yao H,Pan G,Xu GL,Pei D

    更新日期：2013-12-01 00:00:00

  • Mutation of DNASE1 in people with systemic lupus erythematosus.

    abstract：:Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune diseases that causes progressive glomerulonephritis, arthritis and an erythematoid rash. Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome. Here we describe two patients with a heterozygous nonsense mutation in exon 2 o...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/91070

    authors： Yasutomo K,Horiuchi T,Kagami S,Tsukamoto H,Hashimura C,Urushihara M,Kuroda Y

    更新日期：2001-08-01 00:00:00

  • Frequent somatic mutations in MAP3K5 and MAP3K9 in metastatic melanoma identified by exome sequencing.

    abstract：:We sequenced eight melanoma exomes to identify new somatic mutations in metastatic melanoma. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9. Structural modeling predict...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.1041

    authors： Stark MS,Woods SL,Gartside MG,Bonazzi VF,Dutton-Regester K,Aoude LG,Chow D,Sereduk C,Niemi NM,Tang N,Ellis JJ,Reid J,Zismann V,Tyagi S,Muzny D,Newsham I,Wu Y,Palmer JM,Pollak T,Youngkin D,Brooks BR,Lanagan C,S

    更新日期：2011-12-25 00:00:00

  • Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes.

    abstract：:Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.381

    authors： Barrett JC,Clayton DG,Concannon P,Akolkar B,Cooper JD,Erlich HA,Julier C,Morahan G,Nerup J,Nierras C,Plagnol V,Pociot F,Schuilenburg H,Smyth DJ,Stevens H,Todd JA,Walker NM,Rich SS,Type 1 Diabetes Genetics Consortium.

    更新日期：2009-06-01 00:00:00

  • Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia.

    abstract：:Targeting of cancer stem cells is believed to be essential for curative therapy of cancers, but supporting evidence is limited. Few selective target genes in cancer stem cells have been identified. Here we identify the arachidonate 5-lipoxygenase (5-LO) gene (Alox5) as a critical regulator for leukemia stem cells (LSC...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.389

    authors： Chen Y,Hu Y,Zhang H,Peng C,Li S

    更新日期：2009-07-01 00:00:00

  • PHF6 mutations in T-cell acute lymphoblastic leukemia.

    abstract：:Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males. In this study, we report the identification of inactivating mutations and deletions in the...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.542

    authors： Van Vlierberghe P,Palomero T,Khiabanian H,Van der Meulen J,Castillo M,Van Roy N,De Moerloose B,Philippé J,González-García S,Toribio ML,Taghon T,Zuurbier L,Cauwelier B,Harrison CJ,Schwab C,Pisecker M,Strehl S,Langerak AW

    更新日期：2010-04-01 00:00:00

  • Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors.

    abstract：:Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. Here we uniformly analyzed whole-exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinica...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-018-0200-2

    authors： Miao D,Margolis CA,Vokes NI,Liu D,Taylor-Weiner A,Wankowicz SM,Adeegbe D,Keliher D,Schilling B,Tracy A,Manos M,Chau NG,Hanna GJ,Polak P,Rodig SJ,Signoretti S,Sholl LM,Engelman JA,Getz G,Jänne PA,Haddad RI,Chouei

    更新日期：2018-09-01 00:00:00

  • Whole-genome deep-learning analysis identifies contribution of noncoding mutations to autism risk.

    abstract：:We address the challenge of detecting the contribution of noncoding mutations to disease with a deep-learning-based framework that predicts the specific regulatory effects and the deleterious impact of genetic variants. Applying this framework to 1,790 autism spectrum disorder (ASD) simplex families reveals a role in ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-019-0420-0

    authors： Zhou J,Park CY,Theesfeld CL,Wong AK,Yuan Y,Scheckel C,Fak JJ,Funk J,Yao K,Tajima Y,Packer A,Darnell RB,Troyanskaya OG

    更新日期：2019-06-01 00:00:00

  • Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA.

    abstract：:Genetic integrity is crucial to normal cell function, and mutations in genes required for DNA replication and repair underlie various forms of genetic instability and disease, including cancer. One structural feature of intact genomes is runs of homopolymeric dC/dG. Here we describe an unusual mutator phenotype in Cae...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng928

    authors： Cheung I,Schertzer M,Rose A,Lansdorp PM

    更新日期：2002-08-01 00:00:00

  • Another piece of the autism puzzle.

    abstract：:A new study has identified rare de novo mutations in SHANK2 in individuals with autism and/or mental retardation. SHANK2 encodes a scaffolding protein present in excitatory synapses. This finding sheds some light on the pathophysiology of social and cognitive disability. ...

    journal_title：Nature genetics

    pub_type： 评论,新闻

    doi：10.1038/ng0610-478

    authors： State MW

    更新日期：2010-06-01 00:00:00

  • A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family.

    abstract：:Epileptic disorders affect about 20-40 million people worldwide, and 40% of these are idiopathic generalized epilepsies (IGEs; ref. 1). Most of the IGEs that are inherited are complex, multigenic diseases. To address basic mechanisms for epilepsies, we have focused on one well-defined class of IGEs with an autosomal-d...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng0198-53

    authors： Charlier C,Singh NA,Ryan SG,Lewis TB,Reus BE,Leach RJ,Leppert M

    更新日期：1998-01-01 00:00:00

  • Author Correction: PGBD5 promotes site-specific oncogenic mutations in human tumors.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature genetics

    pub_type： 已发布勘误

    doi：10.1038/s41588-020-00711-z

    authors： Henssen AG,Koche R,Zhuang J,Jiang E,Reed C,Eisenberg A,Still E,MacArthur IC,Rodríguez-Fos E,Gonzalez S,Puiggròs M,Blackford AN,Mason CE,de Stanchina E,Gönen M,Emde AK,Shah M,Arora K,Reeves C,Socci ND,Perlman E,A

    更新日期：2020-11-01 00:00:00

  • Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.

    abstract：:We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1122

    authors： Dodé C,Levilliers J,Dupont JM,De Paepe A,Le Dû N,Soussi-Yanicostas N,Coimbra RS,Delmaghani S,Compain-Nouaille S,Baverel F,Pêcheux C,Le Tessier D,Cruaud C,Delpech M,Speleman F,Vermeulen S,Amalfitano A,Bachelot Y,Boucha

    更新日期：2003-04-01 00:00:00

  • Transcription imparts architecture, function and logic to enhancer units.

    abstract：:Distal enhancers play pivotal roles in development and disease yet remain one of the least understood regulatory elements. We used massively parallel reporter assays to perform functional comparisons of two leading enhancer models and find that gene-distal transcription start sites are robust predictors of active enha...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-020-0686-2

    authors： Tippens ND,Liang J,Leung AK,Wierbowski SD,Ozer A,Booth JG,Lis JT,Yu H

    更新日期：2020-10-01 00:00:00

  • Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33.

    abstract：:Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (ca...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.670

    authors： Houlston RS,Cheadle J,Dobbins SE,Tenesa A,Jones AM,Howarth K,Spain SL,Broderick P,Domingo E,Farrington S,Prendergast JG,Pittman AM,Theodoratou E,Smith CG,Olver B,Walther A,Barnetson RA,Churchman M,Jaeger EE,Penegar

    更新日期：2010-11-01 00:00:00

  • Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity.

    abstract：:Hundreds of genes reside in structurally complex, poorly understood regions of the human genome. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity, although genome-wide ass...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3340

    authors： Usher CL,Handsaker RE,Esko T,Tuke MA,Weedon MN,Hastie AR,Cao H,Moon JE,Kashin S,Fuchsberger C,Metspalu A,Pato CN,Pato MT,McCarthy MI,Boehnke M,Altshuler DM,Frayling TM,Hirschhorn JN,McCarroll SA

    更新日期：2015-08-01 00:00:00

  • Extensive allelic variation and ultrashort telomeres in senescent human cells.

    abstract：:By imposing a limit on the proliferative lifespan of most somatic cells, telomere erosion represents an innate mechanism for tumor suppression and may contribute to age-related disease. A detailed understanding of the pathways that link shortened telomeres to replicative senescence has been severely hindered by the in...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1084

    authors： Baird DM,Rowson J,Wynford-Thomas D,Kipling D

    更新日期：2003-02-01 00:00:00

  • Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.

    abstract：:Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding a...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1842

    authors： Crow YJ,Leitch A,Hayward BE,Garner A,Parmar R,Griffith E,Ali M,Semple C,Aicardi J,Babul-Hirji R,Baumann C,Baxter P,Bertini E,Chandler KE,Chitayat D,Cau D,Déry C,Fazzi E,Goizet C,King MD,Klepper J,Lacombe D,Lan

    更新日期：2006-08-01 00:00:00

  • Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.

    abstract：:Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing b...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.3878

    authors： Tchasovnikarova IA,Timms RT,Douse CH,Roberts RC,Dougan G,Kingston RE,Modis Y,Lehner PJ

    更新日期：2017-07-01 00:00:00

  • The neuronal sortilin-related receptor SORL1 is genetically associated with Alzheimer disease.

    abstract：:The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng1943

    authors： Rogaeva E,Meng Y,Lee JH,Gu Y,Kawarai T,Zou F,Katayama T,Baldwin CT,Cheng R,Hasegawa H,Chen F,Shibata N,Lunetta KL,Pardossi-Piquard R,Bohm C,Wakutani Y,Cupples LA,Cuenco KT,Green RC,Pinessi L,Rainero I,Sorbi S,

    更新日期：2007-02-01 00:00:00

  • GRIN2A mutations in acquired epileptic aphasia and related childhood focal epilepsies and encephalopathies with speech and language dysfunction.

    abstract：:Epileptic encephalopathies are severe brain disorders with the epileptic component contributing to the worsening of cognitive and behavioral manifestations. Acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and continuous spike and waves during slow-wave sleep syndrome (CSWSS) represent rare and closely relat...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/ng.2726

    authors： Lesca G,Rudolf G,Bruneau N,Lozovaya N,Labalme A,Boutry-Kryza N,Salmi M,Tsintsadze T,Addis L,Motte J,Wright S,Tsintsadze V,Michel A,Doummar D,Lascelles K,Strug L,Waters P,de Bellescize J,Vrielynck P,de Saint Martin A

    更新日期：2013-09-01 00:00:00

  • Early TP53 alterations engage environmental exposures to promote gastric premalignancy in an integrative mouse model.

    abstract：:Somatic alterations in cancer genes are being detected in normal and premalignant tissue, thus placing greater emphasis on gene-environment interactions that enable disease phenotypes. By combining early genetic alterations with disease-relevant exposures, we developed an integrative mouse model to study gastric prema...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/s41588-019-0574-9

    authors： Sethi NS,Kikuchi O,Duronio GN,Stachler MD,McFarland JM,Ferrer-Luna R,Zhang Y,Bao C,Bronson R,Patil D,Sanchez-Vega F,Liu JB,Sicinska E,Lazaro JB,Ligon KL,Beroukhim R,Bass AJ

    更新日期：2020-02-01 00:00:00

  • Localization to Xq27 of a susceptibility gene for testicular germ-cell tumours.

    abstract：:Testicular germ-cell tumours (TGCT) affect 1 in 500 men and are the most common cancer in males aged 15-40 in Western European populations. The incidence of TGCT has risen dramatically over the last century. Known risk factors for TGCT include a history of undescended testis (UDT), testicular dysgenesis, infertility, ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/72877

    authors： Rapley EA,Crockford GP,Teare D,Biggs P,Seal S,Barfoot R,Edwards S,Hamoudi R,Heimdal K,Fossâ SD,Tucker K,Donald J,Collins F,Friedlander M,Hogg D,Goss P,Heidenreich A,Ormiston W,Daly PA,Forman D,Oliver TD,Leahy M

    更新日期：2000-02-01 00:00:00

  • Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production.

    abstract：:The gene Ucp2 is a member of a family of genes found in animals and plants, encoding a protein homologous to the brown fat uncoupling protein Ucp1 (refs 1-3). As Ucp2 is widely expressed in mammalian tissues, uncouples respiration and resides within a region of genetic linkage to obesity, a role in energy dissipation ...

    journal_title：Nature genetics

    pub_type： 杂志文章

    doi：10.1038/82565

    authors： Arsenijevic D,Onuma H,Pecqueur C,Raimbault S,Manning BS,Miroux B,Couplan E,Alves-Guerra MC,Goubern M,Surwit R,Bouillaud F,Richard D,Collins S,Ricquier D

    更新日期：2000-12-01 00:00:00