The genomic landscape of undifferentiated embryonal sarcoma of the liver is typified by C19MC structural rearrangement and overexpression combined with TP53 mutation or loss.

Abstract:

:Undifferentiated embryonal sarcoma of the liver (UESL) is a rare and aggressive malignancy. Though the molecular underpinnings of this cancer have been largely unexplored, recurrent chromosomal breakpoints affecting a noncoding region on chr19q13, which includes the chromosome 19 microRNA cluster (C19MC), have been reported in several cases. We performed comprehensive molecular profiling on samples from 14 patients diagnosed with UESL. Congruent with prior reports, we identified structural variants in chr19q13 in 10 of 13 evaluable tumors. From whole transcriptome sequencing, we observed striking expressional activity of the entire C19MC region. Concordantly, in 7 of 7 samples undergoing miRNAseq, we observed hyperexpression of the miRNAs within this cluster to levels >100 fold compared to matched normal tissue or a non-C19MC amplified cancer cell line. Concurrent TP53 mutation or copy number loss was identified in all evaluable tumors with evidence of C19MC overexpression. We find that C19MC miRNAs exhibit significant negative correlation to TP53 regulatory miRNAs and K-Ras regulatory miRNAs. Using RNA-seq we identified that pathways relevant to cellular differentiation as well as mRNA translation machinery are transcriptionally enriched in UESL. In summary, utilizing a combination of next-generation sequencing and high-density arrays we identify the combination of C19MC hyperexpression via chromosomal structural event with TP53 mutation or loss as highly recurrent genomic features of UESL.

journal_name

PLoS Genet

journal_title

PLoS genetics

authors

Setty BA,Jinesh GG,Arnold M,Pettersson F,Cheng CH,Cen L,Yoder SJ,Teer JK,Flores ER,Reed DR,Brohl AS

doi

10.1371/journal.pgen.1008642

subject

Has Abstract

pub_date

2020-04-20 00:00:00

pages

e1008642

issue

4

eissn

1553-7390

issn

1553-7404

pii

PGENETICS-D-19-01335

journal_volume

16

pub_type

杂志文章
  • LF4/MOK and a CDK-related kinase regulate the number and length of cilia in Tetrahymena.

    abstract::The length of cilia is controlled by a poorly understood mechanism that involves members of the conserved RCK kinase group, and among them, the LF4/MOK kinases. The multiciliated protist model, Tetrahymena, carries two types of cilia (oral and locomotory) and the length of the locomotory cilia is dependent on their po...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1008099

    authors: Jiang YY,Maier W,Baumeister R,Minevich G,Joachimiak E,Wloga D,Ruan Z,Kannan N,Bocarro S,Bahraini A,Vasudevan KK,Lechtreck K,Orias E,Gaertig J

    更新日期:2019-07-24 00:00:00

  • A role for CF1A 3' end processing complex in promoter-associated transcription.

    abstract::The Cleavage Factor 1A (CF1A) complex, which is required for the termination of transcription in budding yeast, occupies the 3' end of transcriptionally active genes. We recently demonstrated that CF1A subunits also crosslink to the 5' end of genes during transcription. The presence of CF1A complex at the promoter sug...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003722

    authors: Al Husini N,Kudla P,Ansari A

    更新日期:2013-01-01 00:00:00

  • Demographic history of european populations of Arabidopsis thaliana.

    abstract::The model plant species Arabidopsis thaliana is successful at colonizing land that has recently undergone human-mediated disturbance. To investigate the prehistoric spread of A. thaliana, we applied approximate Bayesian computation and explicit spatial modeling to 76 European accessions sequenced at 876 nuclear loci. ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000075

    authors: François O,Blum MG,Jakobsson M,Rosenberg NA

    更新日期:2008-05-16 00:00:00

  • DNA damage as a consequence of NLR activation.

    abstract::DNA damage observed during plant immune responses is reported to be an intrinsic component of plant immunity. However, other immune responses may suppress DNA damage to maintain host genome integrity. Here, we show that immunity-related DNA damage can be abrogated by preventing cell death triggered by Nucleotide-bindi...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007235

    authors: Rodriguez E,Chevalier J,El Ghoul H,Voldum-Clausen K,Mundy J,Petersen M

    更新日期:2018-02-20 00:00:00

  • Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling.

    abstract::Genome-wide transcription start site (TSS) profiles of the enterobacteria Escherichia coli and Klebsiella pneumoniae were experimentally determined through modified 5' RACE followed by deep sequencing of intact primary mRNA. This identified 3,746 and 3,143 TSSs for E. coli and K. pneumoniae, respectively. Experimental...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002867

    authors: Kim D,Hong JS,Qiu Y,Nagarajan H,Seo JH,Cho BK,Tsai SF,Palsson BØ

    更新日期:2012-01-01 00:00:00

  • Gene reactivation by 5-aza-2'-deoxycytidine-induced demethylation requires SRCAP-mediated H2A.Z insertion to establish nucleosome depleted regions.

    abstract::5-Aza-2'-deoxycytidine, approved by the FDA for the treatment of myelodysplastic syndrome (MDS), is incorporated into the DNA of dividing cells where it specifically inhibits DNA methylation by forming covalent complexes with the DNA methyltransferases (DNMTs). In an effort to study the correlations between DNA methyl...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002604

    authors: Yang X,Noushmehr H,Han H,Andreu-Vieyra C,Liang G,Jones PA

    更新日期:2012-01-01 00:00:00

  • Dissemination of cephalosporin resistance genes between Escherichia coli strains from farm animals and humans by specific plasmid lineages.

    abstract::Third-generation cephalosporins are a class of β-lactam antibiotics that are often used for the treatment of human infections caused by Gram-negative bacteria, especially Escherichia coli. Worryingly, the incidence of human infections caused by third-generation cephalosporin-resistant E. coli is increasing worldwide. ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004776

    authors: de Been M,Lanza VF,de Toro M,Scharringa J,Dohmen W,Du Y,Hu J,Lei Y,Li N,Tooming-Klunderud A,Heederik DJ,Fluit AC,Bonten MJ,Willems RJ,de la Cruz F,van Schaik W

    更新日期:2014-12-18 00:00:00

  • Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury.

    abstract::Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and l...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007070

    authors: Quattrocelli M,Capote J,Ohiri JC,Warner JL,Vo AH,Earley JU,Hadhazy M,Demonbreun AR,Spencer MJ,McNally EM

    更新日期:2017-10-24 00:00:00

  • Loss of hepatocyte cell division leads to liver inflammation and fibrosis.

    abstract::The liver possesses a remarkable regenerative capacity based partly on the ability of hepatocytes to re-enter the cell cycle and divide to replace damaged cells. This capability is substantially reduced upon chronic damage, but it is not clear if this is a cause or consequence of liver disease. Here, we investigate wh...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1009084

    authors: Dewhurst MR,Ow JR,Zafer G,van Hul NKM,Wollmann H,Bisteau X,Brough D,Choi H,Kaldis P

    更新日期:2020-11-04 00:00:00

  • Human social genomics.

    abstract::A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differenti...

    journal_title:PLoS genetics

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pgen.1004601

    authors: Cole SW

    更新日期:2014-08-28 00:00:00

  • Convergence of Light and ABA signaling on the ABI5 promoter.

    abstract::Light is one of the most important environmental cues regulating multiple aspects of plant growth and development, and abscisic acid (ABA) is a plant hormone that plays important roles during many phases of the plant life cycle and in plants' responses to various environmental stresses. How plants integrate the extern...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004197

    authors: Xu D,Li J,Gangappa SN,Hettiarachchi C,Lin F,Andersson MX,Jiang Y,Deng XW,Holm M

    更新日期:2014-02-27 00:00:00

  • Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes.

    abstract::Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigat...

    journal_title:PLoS genetics

    pub_type: 杂志文章,meta分析

    doi:10.1371/journal.pgen.1004517

    authors: Ng MC,Shriner D,Chen BH,Li J,Chen WM,Guo X,Liu J,Bielinski SJ,Yanek LR,Nalls MA,Comeau ME,Rasmussen-Torvik LJ,Jensen RA,Evans DS,Sun YV,An P,Patel SR,Lu Y,Long J,Armstrong LL,Wagenknecht L,Yang L,Snively BM,

    更新日期:2014-08-07 00:00:00

  • Adaptation to High Ethanol Reveals Complex Evolutionary Pathways.

    abstract::Tolerance to high levels of ethanol is an ecologically and industrially relevant phenotype of microbes, but the molecular mechanisms underlying this complex trait remain largely unknown. Here, we use long-term experimental evolution of isogenic yeast populations of different initial ploidy to study adaptation to incre...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005635

    authors: Voordeckers K,Kominek J,Das A,Espinosa-Cantú A,De Maeyer D,Arslan A,Van Pee M,van der Zande E,Meert W,Yang Y,Zhu B,Marchal K,DeLuna A,Van Noort V,Jelier R,Verstrepen KJ

    更新日期:2015-11-06 00:00:00

  • Coevolution of interacting fertilization proteins.

    abstract::Reproductive proteins are among the fastest evolving in the proteome, often due to the consequences of positive selection, and their rapid evolution is frequently attributed to a coevolutionary process between interacting female and male proteins. Such a process could leave characteristic signatures at coevolving gene...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000570

    authors: Clark NL,Gasper J,Sekino M,Springer SA,Aquadro CF,Swanson WJ

    更新日期:2009-07-01 00:00:00

  • Cellular variability of RpoS expression underlies subpopulation activation of an integrative and conjugative element.

    abstract::Conjugative transfer of the integrative and conjugative element ICEclc in the bacterium Pseudomonas knackmussii is the consequence of a bistable decision taken in some 3% of cells in a population during stationary phase. Here we study the possible control exerted by the stationary phase sigma factor RpoS on the bistab...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002818

    authors: Miyazaki R,Minoia M,Pradervand N,Sulser S,Reinhard F,van der Meer JR

    更新日期:2012-01-01 00:00:00

  • Bacterial adaptation through loss of function.

    abstract::The metabolic capabilities and regulatory networks of bacteria have been optimized by evolution in response to selective pressures present in each species' native ecological niche. In a new environment, however, the same bacteria may grow poorly due to regulatory constraints or biochemical deficiencies. Adaptation to ...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003617

    authors: Hottes AK,Freddolino PL,Khare A,Donnell ZN,Liu JC,Tavazoie S

    更新日期:2013-01-01 00:00:00

  • Female bias in Rhox6 and 9 regulation by the histone demethylase KDM6A.

    abstract::The Rhox cluster on the mouse X chromosome contains reproduction-related homeobox genes expressed in a sexually dimorphic manner. We report that two members of the Rhox cluster, Rhox6 and 9, are regulated by de-methylation of histone H3 at lysine 27 by KDM6A, a histone demethylase with female-biased expression. Consis...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1003489

    authors: Berletch JB,Deng X,Nguyen DK,Disteche CM

    更新日期:2013-05-01 00:00:00

  • Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis.

    abstract::In mammalian meiosis, homologous chromosome synapsis is coupled with recombination. As in most eukaryotes, mammalian meiocytes have checkpoints that monitor the fidelity of these processes. We report that the mouse ortholog (Trip13) of pachytene checkpoint 2 (PCH2), an essential component of the synapsis checkpoint in...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.0030130

    authors: Li XC,Schimenti JC

    更新日期:2007-08-01 00:00:00

  • Attenuation of the sensing capabilities of PhoQ in transition to obligate insect-bacterial association.

    abstract::Sodalis glossinidius, a maternally inherited endosymbiont of the tsetse fly, maintains genes encoding homologues of the PhoP-PhoQ two-component regulatory system. This two-component system has been extensively studied in facultative bacterial pathogens and is known to serve as an environmental magnesium sensor and a r...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002349

    authors: Pontes MH,Smith KL,De Vooght L,Van Den Abbeele J,Dale C

    更新日期:2011-11-01 00:00:00

  • Re-patterning sleep architecture in Drosophila through gustatory perception and nutritional quality.

    abstract::Organisms perceive changes in their dietary environment and enact a suite of behavioral and metabolic adaptations that can impact motivational behavior, disease resistance, and longevity. However, the precise nature and mechanism of these dietary responses is not known. We have uncovered a novel link between dietary f...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1002668

    authors: Linford NJ,Chan TP,Pletcher SD

    更新日期:2012-01-01 00:00:00

  • Evolutionary constraint and disease associations of post-translational modification sites in human genomes.

    abstract::Interpreting the impact of human genome variation on phenotype is challenging. The functional effect of protein-coding variants is often predicted using sequence conservation and population frequency data, however other factors are likely relevant. We hypothesized that variants in protein post-translational modificati...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004919

    authors: Reimand J,Wagih O,Bader GD

    更新日期:2015-01-22 00:00:00

  • Vestigialization of an allosteric switch: genetic and structural mechanisms for the evolution of constitutive activity in a steroid hormone receptor.

    abstract::An important goal in molecular evolution is to understand the genetic and physical mechanisms by which protein functions evolve and, in turn, to characterize how a protein's physical architecture influences its evolution. Here we dissect the mechanisms for an evolutionary shift in function in the mollusk ortholog of t...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004058

    authors: Bridgham JT,Keay J,Ortlund EA,Thornton JW

    更新日期:2014-01-01 00:00:00

  • Silencing is noisy: population and cell level noise in telomere-adjacent genes is dependent on telomere position and sir2.

    abstract::Cell-to-cell gene expression noise is thought to be an important mechanism for generating phenotypic diversity. Furthermore, telomeric regions are major sites for gene amplification, which is thought to drive genetic diversity. Here we found that individual subtelomeric TLO genes exhibit increased variation in transcr...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1004436

    authors: Anderson MZ,Gerstein AC,Wigen L,Baller JA,Berman J

    更新日期:2014-07-24 00:00:00

  • What Is the Tree of Life?

    abstract::A universal Tree of Life (TOL) has long been a goal of molecular phylogeneticists, but reticulation at the level of genes and possibly at the levels of cells and species renders any simple interpretation of such a TOL, especially as applied to prokaryotes, problematic. ...

    journal_title:PLoS genetics

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pgen.1005912

    authors: Doolittle WF,Brunet TD

    更新日期:2016-04-14 00:00:00

  • Human MLH1 protein participates in genomic damage checkpoint signaling in response to DNA interstrand crosslinks, while MSH2 functions in DNA repair.

    abstract::DNA interstrand crosslinks (ICLs) are among the most toxic types of damage to a cell. For this reason, many ICL-inducing agents are effective therapeutic agents. For example, cisplatin and nitrogen mustards are used for treating cancer and psoralen plus UVA (PUVA) is useful for treating psoriasis. However, repair mech...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000189

    authors: Wu Q,Vasquez KM

    更新日期:2008-09-12 00:00:00

  • Regulation of Gap Junction Dynamics by UNC-44/ankyrin and UNC-33/CRMP through VAB-8 in C. elegans Neurons.

    abstract::Gap junctions are present in both vertebrates and invertebrates from nematodes to mammals. Although the importance of gap junctions has been documented in many biological processes, the molecular mechanisms underlying gap junction dynamics remain unclear. Here, using the C. elegans PLM neurons as a model, we show that...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005948

    authors: Meng L,Chen CH,Yan D

    更新日期:2016-03-25 00:00:00

  • Nonredundant requirement for multiple histone modifications for the early anaphase release of the mitotic exit regulator Cdc14 from nucleolar chromatin.

    abstract::In Saccharomyces cerevisiae, the conserved phosphatase Cdc14 is required for the exit from mitosis. It is anchored on nucleolar chromatin by the Cfi1/Net1 protein until early anaphase, at which time it is released into the nucleoplasm. Two poorly understood, redundant pathways promote Cdc14 release, the FEAR (Cdc four...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000588

    authors: Hwang WW,Madhani HD

    更新日期:2009-08-01 00:00:00

  • Reproductive Aging Drives Protein Accumulation in the Uterus and Limits Lifespan in C. elegans.

    abstract::Aging in Caenorhabditis elegans is characterized by widespread physiological and molecular changes, but the mechanisms that determine the rate at which these changes occur are not well understood. In this study, we identify a novel link between reproductive aging and somatic aging in C. elegans. By measuring global ag...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1005725

    authors: Zimmerman SM,Hinkson IV,Elias JE,Kim SK

    更新日期:2015-12-11 00:00:00

  • Coordinated regulation of Arabidopsis microRNA biogenesis and red light signaling through Dicer-like 1 and phytochrome-interacting factor 4.

    abstract::Light and microRNAs (miRNAs) are key external and internal signals for plant development, respectively. However, the relationship between the light signaling and miRNA biogenesis pathways remains unknown. Here we found that miRNA processer proteins DCL1 and HYL1 interact with a basic helix-loop-helix (bHLH) transcript...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1007247

    authors: Sun Z,Li M,Zhou Y,Guo T,Liu Y,Zhang H,Fang Y

    更新日期:2018-03-09 00:00:00

  • Variation in molybdenum content across broadly distributed populations of Arabidopsis thaliana is controlled by a mitochondrial molybdenum transporter (MOT1).

    abstract::Molybdenum (Mo) is an essential micronutrient for plants, serving as a cofactor for enzymes involved in nitrate assimilation, sulfite detoxification, abscisic acid biosynthesis, and purine degradation. Here we show that natural variation in shoot Mo content across 92 Arabidopsis thaliana accessions is controlled by va...

    journal_title:PLoS genetics

    pub_type: 杂志文章

    doi:10.1371/journal.pgen.1000004

    authors: Baxter I,Muthukumar B,Park HC,Buchner P,Lahner B,Danku J,Zhao K,Lee J,Hawkesford MJ,Guerinot ML,Salt DE

    更新日期:2008-02-29 00:00:00