Comparative methylome analysis of benign and malignant peripheral nerve sheath tumors.


:Aberrant DNA methylation (DNAm) was first linked to cancer over 25 yr ago. Since then, many studies have associated hypermethylation of tumor suppressor genes and hypomethylation of oncogenes to the tumorigenic process. However, most of these studies have been limited to the analysis of promoters and CpG islands (CGIs). Recently, new technologies for whole-genome DNAm (methylome) analysis have been developed, enabling unbiased analysis of cancer methylomes. By using MeDIP-seq, we report a sequencing-based comparative methylome analysis of malignant peripheral nerve sheath tumors (MPNSTs), benign neurofibromas, and normal Schwann cells. Analysis of these methylomes revealed a complex landscape of DNAm alterations. In contrast to what has been reported for other tumor types, no significant global hypomethylation was observed in MPNSTs using methylome analysis by MeDIP-seq. However, a highly significant (P < 10(-100)) directional difference in DNAm was found in satellite repeats, suggesting these repeats to be the main target for hypomethylation in MPNSTs. Comparative analysis of the MPNST and Schwann cell methylomes identified 101,466 cancer-associated differentially methylated regions (cDMRs). Analysis showed these cDMRs to be significantly enriched for two satellite repeat types (SATR1 and ARLα) and suggests an association between aberrant DNAm of these sequences and transition from healthy cells to malignant disease. Significant enrichment of hypermethylated cDMRs in CGI shores (P < 10(-60)), non-CGI-associated promoters (P < 10(-4)) and hypomethylated cDMRs in SINE repeats (P < 10(-100)) was also identified. Integration of DNAm and gene expression data showed that the expression pattern of genes associated with CGI shore cDMRs was able to discriminate between disease phenotypes. This study establishes MeDIP-seq as an effective method to analyze cancer methylomes.


Genome Res


Genome research


Feber A,Wilson GA,Zhang L,Presneau N,Idowu B,Down TA,Rakyan VK,Noon LA,Lloyd AC,Stupka E,Schiza V,Teschendorff AE,Schroth GP,Flanagan A,Beck S




Has Abstract


2011-04-01 00:00:00














  • Identification of protein features encoded by alternative exons using Exon Ontology.

    abstract::Transcriptomic genome-wide analyses demonstrate massive variation of alternative splicing in many physiological and pathological situations. One major challenge is now to establish the biological contribution of alternative splicing variation in physiological- or pathological-associated cellular phenotypes. Toward thi...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Tranchevent LC,Aubé F,Dulaurier L,Benoit-Pilven C,Rey A,Poret A,Chautard E,Mortada H,Desmet FO,Chakrama FZ,Moreno-Garcia MA,Goillot E,Janczarski S,Mortreux F,Bourgeois CF,Auboeuf D

    更新日期:2017-06-01 00:00:00

  • The nonessentiality of essential genes in yeast provides therapeutic insights into a human disease.

    abstract::Essential genes refer to those whose null mutation leads to lethality or sterility. Theoretical reasoning and empirical data both suggest that the fatal effect of inactivating an essential gene can be attributed to either the loss of indispensable core cellular function (Type I), or the gain of fatal side effects afte...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Chen P,Wang D,Chen H,Zhou Z,He X

    更新日期:2016-10-01 00:00:00

  • Translation initiation downstream from annotated start codons in human mRNAs coevolves with the Kozak context.

    abstract::Eukaryotic translation initiation involves preinitiation ribosomal complex 5'-to-3' directional probing of mRNA for codons suitable for starting protein synthesis. The recognition of codons as starts depends on the codon identity and on its immediate nucleotide context known as Kozak context. When the context is weak ...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Benitez-Cantos MS,Yordanova MM,O'Connor PBF,Zhdanov AV,Kovalchuk SI,Papkovsky DB,Andreev DE,Baranov PV

    更新日期:2020-07-01 00:00:00

  • Parente2: a fast and accurate method for detecting identity by descent.

    abstract::Identity-by-descent (IBD) inference is the problem of establishing a genetic connection between two individuals through a genomic segment that is inherited by both individuals from a recent common ancestor. IBD inference is an important preceding step in a variety of population genomic studies, ranging from demographi...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Rodriguez JM,Bercovici S,Huang L,Frostig R,Batzoglou S

    更新日期:2015-02-01 00:00:00

  • Genome-scale identification of cellular pathways required for cell surface recognition.

    abstract::Interactions mediated by cell surface receptors initiate important instructive signaling cues but can be difficult to detect in biochemical assays because they are often highly transient and membrane-embedded receptors are difficult to solubilize in their native conformation. Here, we address these biochemical challen...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Sharma S,Bartholdson SJ,Couch ACM,Yusa K,Wright GJ

    更新日期:2018-09-01 00:00:00

  • Rapid molecular assays to study human centromere genomics.

    abstract::The centromere is the structural unit responsible for the faithful segregation of chromosomes. Although regulation of centromeric function by epigenetic factors has been well-studied, the contributions of the underlying DNA sequences have been much less well defined, and existing methodologies for studying centromere ...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Contreras-Galindo R,Fischer S,Saha AK,Lundy JD,Cervantes PW,Mourad M,Wang C,Qian B,Dai M,Meng F,Chinnaiyan A,Omenn GS,Kaplan MH,Markovitz DM

    更新日期:2017-12-01 00:00:00

  • Transcription factor binding and modified histones in human bidirectional promoters.

    abstract::Bidirectional promoters have received considerable attention because of their ability to regulate two downstream genes (divergent genes). They are also highly abundant, directing the transcription of approximately 11% of genes in the human genome. We categorized the presence of DNA sequence motifs, binding of transcri...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Lin JM,Collins PJ,Trinklein ND,Fu Y,Xi H,Myers RM,Weng Z

    更新日期:2007-06-01 00:00:00

  • The landscape of histone modifications across 1% of the human genome in five human cell lines.

    abstract::We generated high-resolution maps of histone H3 lysine 9/14 acetylation (H3ac), histone H4 lysine 5/8/12/16 acetylation (H4ac), and histone H3 at lysine 4 mono-, di-, and trimethylation (H3K4me1, H3K4me2, H3K4me3, respectively) across the ENCODE regions. Studying each modification in five human cell lines including th...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Koch CM,Andrews RM,Flicek P,Dillon SC,Karaöz U,Clelland GK,Wilcox S,Beare DM,Fowler JC,Couttet P,James KD,Lefebvre GC,Bruce AW,Dovey OM,Ellis PD,Dhami P,Langford CF,Weng Z,Birney E,Carter NP,Vetrie D,Dunham I

    更新日期:2007-06-01 00:00:00

  • Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay.

    abstract::Large-scale genetic studies are highly dependent on efficient and scalable multiplex SNP assays. In this study, we report the development of Molecular Inversion Probe technology with four-color, single array detection, applied to large-scale genotyping of up to 12,000 SNPs per reaction. While generating 38,429 SNP ass...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Hardenbol P,Yu F,Belmont J,Mackenzie J,Bruckner C,Brundage T,Boudreau A,Chow S,Eberle J,Erbilgin A,Falkowski M,Fitzgerald R,Ghose S,Iartchouk O,Jain M,Karlin-Neumann G,Lu X,Miao X,Moore B,Moorhead M,Namsaraev E,

    更新日期:2005-02-01 00:00:00

  • A matter of life or death: how microsatellites emerge in and vanish from the human genome.

    abstract::Microsatellites--tandem repeats of short DNA motifs--are abundant in the human genome and have high mutation rates. While microsatellite instability is implicated in numerous genetic diseases, the molecular processes involved in their emergence and disappearance are still not well understood. Microsatellites are hypot...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Kelkar YD,Eckert KA,Chiaromonte F,Makova KD

    更新日期:2011-12-01 00:00:00

  • Genomic organization of the sex-determining and adjacent regions of the sex chromosomes of medaka.

    abstract::Sequencing of the human Y chromosome has uncovered the peculiarities of the genomic organization of a heterogametic sex chromosome of old evolutionary age, and has led to many insights into the evolutionary changes that occurred during its long history. We have studied the genomic organization of the medaka fish Y chr...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Kondo M,Hornung U,Nanda I,Imai S,Sasaki T,Shimizu A,Asakawa S,Hori H,Schmid M,Shimizu N,Schartl M

    更新日期:2006-07-01 00:00:00

  • Schizosaccharomyces pombe essential genes: a pilot study.

    abstract::After completion of the Schizosaccharomyces pombe genome sequence, we have carried out a pilot gene deletion project to assess the feasibility of a genome-wide deletion project and to estimate the percentage of essential genes. Using a PCR-based gene deletion procedure, we investigated 100 genes within a 253-kb region...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Decottignies A,Sanchez-Perez I,Nurse P

    更新日期:2003-03-01 00:00:00

  • Systematic identification of novel protein domain families associated with nuclear functions.

    abstract::A systematic computational analysis of protein sequences containing known nuclear domains led to the identification of 28 novel domain families. This represents a 26% increase in the starting set of 107 known nuclear domain families used for the analysis. Most of the novel domains are present in all major eukaryotic l...

    journal_title:Genome research

    pub_type: 信件


    authors: Doerks T,Copley RR,Schultz J,Ponting CP,Bork P

    更新日期:2002-01-01 00:00:00

  • Pervasive polymorphic imprinted methylation in the human placenta.

    abstract::The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are establish...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Hanna CW,Peñaherrera MS,Saadeh H,Andrews S,McFadden DE,Kelsey G,Robinson WP

    更新日期:2016-06-01 00:00:00

  • Modeling of epigenome dynamics identifies transcription factors that mediate Polycomb targeting.

    abstract::Although changes in chromatin are integral to transcriptional reprogramming during cellular differentiation, it is currently unclear how chromatin modifications are targeted to specific loci. To systematically identify transcription factors (TFs) that can direct chromatin changes during cell fate decisions, we model t...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Arnold P,Schöler A,Pachkov M,Balwierz PJ,Jørgensen H,Stadler MB,van Nimwegen E,Schübeler D

    更新日期:2013-01-01 00:00:00

  • Construction of a genome-scale structural map at single-nucleotide resolution.

    abstract::Few methods are available for mapping the local structure of DNA throughout a genome. The hydroxyl radical cleavage pattern is a measure of the local variation in solvent-accessible surface area of duplex DNA, and thus provides information on the local shape and structure of DNA. We report the construction of a relati...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Greenbaum JA,Pang B,Tullius TD

    更新日期:2007-06-01 00:00:00

  • H3K27me3 forms BLOCs over silent genes and intergenic regions and specifies a histone banding pattern on a mouse autosomal chromosome.

    abstract::In mammals, genome-wide chromatin maps and immunofluorescence studies show that broad domains of repressive histone modifications are present on pericentromeric and telomeric repeats and on the inactive X chromosome. However, only a few autosomal loci such as silent Hox gene clusters have been shown to lie in broad do...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Pauler FM,Sloane MA,Huang R,Regha K,Koerner MV,Tamir I,Sommer A,Aszodi A,Jenuwein T,Barlow DP

    更新日期:2009-02-01 00:00:00

  • Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.

    abstract::By analyzing 1,780,295 5'-end sequences of human full-length cDNAs derived from 164 kinds of oligo-cap cDNA libraries, we identified 269,774 independent positions of transcriptional start sites (TSSs) for 14,628 human RefSeq genes. These TSSs were clustered into 30,964 clusters that were separated from each other by m...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Kimura K,Wakamatsu A,Suzuki Y,Ota T,Nishikawa T,Yamashita R,Yamamoto J,Sekine M,Tsuritani K,Wakaguri H,Ishii S,Sugiyama T,Saito K,Isono Y,Irie R,Kushida N,Yoneyama T,Otsuka R,Kanda K,Yokoi T,Kondo H,Wagatsuma M

    更新日期:2006-01-01 00:00:00

  • Genome-reconstruction for eukaryotes from complex natural microbial communities.

    abstract::Microbial eukaryotes are integral components of natural microbial communities, and their inclusion is critical for many ecosystem studies, yet the majority of published metagenome analyses ignore eukaryotes. In order to include eukaryotes in environmental studies, we propose a method to recover eukaryotic genomes from...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: West PT,Probst AJ,Grigoriev IV,Thomas BC,Banfield JF

    更新日期:2018-04-01 00:00:00

  • A model for postzygotic mosaicisms quantifies the allele fraction drift, mutation rate, and contribution to de novo mutations.

    abstract::The allele fraction (AF) distribution, occurrence rate, and evolutionary contribution of postzygotic single-nucleotide mosaicisms (pSNMs) remain largely unknown. In this study, we developed a mathematical model to describe the accumulation and AF drift of pSNMs during the development of multicellular organisms. By app...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Ye AY,Dou Y,Yang X,Wang S,Huang AY,Wei L

    更新日期:2018-07-01 00:00:00

  • Integrated single-cell genetic and transcriptional analysis suggests novel drivers of chronic lymphocytic leukemia.

    abstract::Intra-tumoral genetic heterogeneity has been characterized across cancers by genome sequencing of bulk tumors, including chronic lymphocytic leukemia (CLL). In order to more accurately identify subclones, define phylogenetic relationships, and probe genotype-phenotype relationships, we developed methods for targeted m...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Wang L,Fan J,Francis JM,Georghiou G,Hergert S,Li S,Gambe R,Zhou CW,Yang C,Xiao S,Cin PD,Bowden M,Kotliar D,Shukla SA,Brown JR,Neuberg D,Alessi DR,Zhang CZ,Kharchenko PV,Livak KJ,Wu CJ

    更新日期:2017-08-01 00:00:00

  • A palindromic structure in the pericentromeric region of various human chromosomes.

    abstract::The primate-specific multisequence family chAB4 is represented with approximately 40 copies within the haploid human genome. Former analyis revealed that unusually long repetition units ( > 35 kb) are distributed to at least eight different chromosomal loci. Remarkably varying copy-numbers within the genomes of closel...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Wöhr G,Fink T,Assum G

    更新日期:1996-04-01 00:00:00

  • Pathway Processor: a tool for integrating whole-genome expression results into metabolic networks.

    abstract::We have developed a new tool to visualize expression data on metabolic pathways and to evaluate which metabolic pathways are most affected by transcriptional changes in whole-genome expression experiments. Using the Fisher Exact Test, the method scores biochemical pathways according to the probability that as many or ...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Grosu P,Townsend JP,Hartl DL,Cavalieri D

    更新日期:2002-07-01 00:00:00

  • Transcriptional alterations in glioma result primarily from DNA methylation-independent mechanisms.

    abstract::In cancer cells, aberrant DNA methylation is commonly associated with transcriptional alterations, including silencing of tumor suppressor genes. However, multiple epigenetic mechanisms, including polycomb repressive marks, contribute to gene deregulation in cancer. To dissect the relative contribution of DNA methylat...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Court F,Le Boiteux E,Fogli A,Müller-Barthélémy M,Vaurs-Barrière C,Chautard E,Pereira B,Biau J,Kemeny JL,Khalil T,Karayan-Tapon L,Verrelle P,Arnaud P

    更新日期:2019-10-01 00:00:00

  • Murine single-cell RNA-seq reveals cell-identity- and tissue-specific trajectories of aging.

    abstract::Aging is a pleiotropic process affecting many aspects of mammalian physiology. Mammals are composed of distinct cell type identities and tissue environments, but the influence of these cell identities and environments on the trajectory of aging in individual cells remains unclear. Here, we performed single-cell RNA-se...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Kimmel JC,Penland L,Rubinstein ND,Hendrickson DG,Kelley DR,Rosenthal AZ

    更新日期:2019-12-01 00:00:00

  • The ClinSeq Project: piloting large-scale genome sequencing for research in genomic medicine.

    abstract::ClinSeq is a pilot project to investigate the use of whole-genome sequencing as a tool for clinical research. By piloting the acquisition of large amounts of DNA sequence data from individual human subjects, we are fostering the development of hypothesis-generating approaches for performing research in genomic medicin...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Biesecker LG,Mullikin JC,Facio FM,Turner C,Cherukuri PF,Blakesley RW,Bouffard GG,Chines PS,Cruz P,Hansen NF,Teer JK,Maskeri B,Young AC,NISC Comparative Sequencing Program.,Manolio TA,Wilson AF,Finkel T,Hwang P,Arai A

    更新日期:2009-09-01 00:00:00

  • GeneID in Drosophila.

    abstract::GeneID is a program to predict genes in anonymous genomic sequences designed with a hierarchical structure. In the first step, splice sites, and start and stop codons are predicted and scored along the sequence using position weight matrices (PWMs). In the second step, exons are built from the sites. Exons are scored ...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Parra G,Blanco E,Guigó R

    更新日期:2000-04-01 00:00:00

  • High resolution mapping of modified DNA nucleobases using excision repair enzymes.

    abstract::The incorporation and creation of modified nucleobases in DNA have profound effects on genome function. We describe methods for mapping positions and local content of modified DNA nucleobases in genomic DNA. We combined in vitro nucleobase excision with massively parallel DNA sequencing (Excision-seq) to determine the...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Bryan DS,Ransom M,Adane B,York K,Hesselberth JR

    更新日期:2014-09-01 00:00:00

  • Long RT-PCR of the entire 8.5-kb NF1 open reading frame and mutation detection on agarose gels.

    abstract::Previous approaches to mutation detection in mRNA from the neurofibromatosis 1 (NF1) locus have required the PCR amplification of five or more overlapping cDNA segments to screen the entire 8.5-kb open reading frame (ORF). Systematically, these assays do not detect deletions that span the region of overlap (usually 1-...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Martinez JM,Breidenbach HH,Cawthon R

    更新日期:1996-01-01 00:00:00

  • Thermophilic bacteria strictly obey Szybalski's transcription direction rule and politely purine-load RNAs with both adenine and guanine.

    abstract::When transcription is to the right of the promoter, the "top," mRNA-synonymous strand of DNA tends to be purine-rich. When transcription is to the left of the promoter, the top, mRNA-template strand tends to be pyrimidine-rich. This transcription-direction rule suggests that there has been an evolutionary selection pr...

    journal_title:Genome research

    pub_type: 杂志文章


    authors: Lao PJ,Forsdyke DR

    更新日期:2000-02-01 00:00:00