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Identification of Therapeutic Targets in Rhabdomyosarcoma through Integrated Genomic, Epigenomic, and Proteomic Analyses.

Cancer cell | 2018

Personalized cancer therapy targeting somatic mutations in patient tumors is increasingly being incorporated into practice. Other therapeutic vulnerabilities resulting from changes in gene expression due to tumor specific epigenetic perturbations are progressively being recognized. These genomic and epigenomic changes are ultimately manifest in the tumor proteome and phosphoproteome. We integrated transcriptomic, epigenomic, and proteomic/phosphoproteomic data to elucidate the cellular origins and therapeutic vulnerabilities of rhabdomyosarcoma (RMS). We discovered that alveolar RMS occurs further along the developmental program than embryonal RMS. We also identified deregulation of the RAS/MEK/ERK/CDK4/6, G2/M, and unfolded protein response pathways through our integrated analysis. Comprehensive preclinical testing revealed that targeting the WEE1 kinase in the G2/M pathway is the most effective approach in vivo for high-risk RMS.

Pubmed ID: 30146332 RIS Download

Additional research tools detected in this publication

None found

Antibodies used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA219686
  • Agency: NEI NIH HHS, United States
    Id: R01 EY018599
  • Agency: NEI NIH HHS, United States
    Id: R01 EY014867
  • Agency: NCI NIH HHS, United States
    Id: R01 CA168875
  • Agency: NCI NIH HHS, United States
    Id: P30 CA021765
  • Agency: Howard Hughes Medical Institute, United States
  • Agency: NIA NIH HHS, United States
    Id: R01 AG047928

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This is a list of tools and resources that we have found mentioned in this publication.


HSP70 Antibody (antibody)

RRID:AB_2279841

This polyclonal targets HSP70

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Cdk4 (C-22) (antibody)

RRID:AB_631219

This polyclonal targets CDK4

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Cdk6 (B-10) (antibody)

RRID:AB_627242

This monoclonal targets Human CDK6

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cyclin D2 (M-20) (antibody)

RRID:AB_2070794

This monoclonal targets Raised against peptide corresponding to an AA sequence at the C-terminus of mouse origin

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Cyclin D3 (DCS22) Mouse mAb (antibody)

RRID:AB_2070801

This monoclonal targets Cyclin D3 (DCS22) Mouse mAb

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Phospho-Rb (Ser795) Antibody (antibody)

RRID:AB_330013

This polyclonal targets Phospho-Rb (Ser795)

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Myogenin (antibody)

RRID:AB_2250893

This monoclonal targets Myogenin

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Myf5 antibody [EPR4899] (antibody)

RRID:AB_10975611

This monoclonal targets Myf5 antibody [EPR4899]

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cdc25C (5H9) Rabbit mAb (antibody)

RRID:AB_560956

This monoclonal targets cdc25C (5H9) Rabbit mAb

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Phospho-S6 Ribosomal Protein (Ser235/236) Antibody (antibody)

RRID:AB_331679

This polyclonal targets Phospho-S6 Ribosomal Protein (Ser235/236)

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HMGA2 Antibody (antibody)

RRID:AB_10694917

This polyclonal targets HMGA2

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nNOS Antibody (antibody)

RRID:AB_2152488

This polyclonal targets Nos1

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POLR2AphosphoS2-human (antibody)

RRID:AB_304749

This polyclonal targets POLR2AphosphoS2

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CTCF-human (antibody)

RRID:AB_2614975

This unknown targets CTCF

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H3K9me3-human (antibody)

RRID:AB_2532132

This polyclonal targets H3K9me3

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H3K9me3 (Human,Mouse) (Host:Rabbit) (antibody)

RRID:AB_11180319

This polyclonal targets H3K9me3 (HumanMouse) (Host:Rabbit)

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H3K36me3-human (antibody)

RRID:AB_306966

This polyclonal targets H3K36me3

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H3K36me3-human (antibody)

RRID:AB_2615073

This unknown targets H3K36me3

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H3K9/14ac polyclonal antibody (antibody)

RRID:AB_2637059

This polyclonal targets H3K9/14ac

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H3K9acK14ac Polyclonal Antibody (antibody)

RRID:AB_2533861

This unknown targets H3K9acK14ac

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Histone H3K27ac antibody (antibody)

RRID:AB_2722569

This polyclonal targets H3K27ac

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H3K27ac-human (antibody)

RRID:AB_2118291

This polyclonal targets H3K27ac

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H3K4me3-dmelanogaster (antibody)

RRID:AB_2615077

This unknown targets H3K4me3

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H3K4me3-human (antibody)

RRID:AB_2616052

This polyclonal targets H3K4me3

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H3K4me2-human (antibody)

RRID:AB_2560996

This polyclonal targets H3K4me2

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H3K4me2-human (antibody)

RRID:AB_2614985

This unknown targets H3K4me2

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H3K4me1-human (antibody)

RRID:AB_2615075

This unknown targets H3K4me1

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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Gene Set Enrichment Analysis (software resource)

RRID:SCR_003199

Software package for interpreting gene expression data. Used for interpretation of a large-scale experiment by identifying pathways and processes.

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Weighted Gene Co-expression Network Analysis (software resource)

RRID:SCR_003302

Software R package for weighted correlation network analysis. WGCNA is also available as point-and-click application. Unfortunately this application is not maintained anymore. It is known to have compatibility problems with R-2.8.x and newer, and the methods it implements are not all state of the art.

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LIMMA (software resource)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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BSMAP (software resource)

RRID:SCR_005671

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 18,2023. Short reads mapping software for bisulfite sequencing reads.

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Bis-SNP (software resource)

RRID:SCR_005439

A software package based on the Genome Analysis Toolkit (GATK) map-reduce framework for genotyping and accurate DNA methylation calling in bisulfite treated massively parallel sequencing (Bisulfite-seq, NOMe-seq, RRBS and any other bisulfite treated sequencing) with Illumina directional library protocol. It contains the following key features: * Call and summarize methylation of any cytosine context provided (CpG, CHH, CHG, GCH et.al.); * Work for single end and paired-end data; * Accurtae variant detection. Enable base quality recalibration and indel calling in bisulfite sequencing; * Based on Java map-reduce framework, allow multi-thread computing. Cross-platform; * Allow multiple output format, detailed VCF files, CpG haplotype reads file for mono-allelic methylation analysis, simplified bedGraph, wig and bed format for visualization in UCSC genome broswer and IGV browser. BisSNP uses bayesian inference with locus specific methylation probabilities and bisulfite conversion rate of different cytosine context(not only CpG, CHH, CHG in Bisulfite-seq, but also GCH et.al. in other bisulfite treated sequencing) to determine genotypes and methylation levels simultaneously.

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Integrative Genomics Viewer (software resource)

RRID:SCR_011793

A high-performance visualization tool for interactive exploration of large, integrated genomic datasets.

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SAMTOOLS (software resource)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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Picard (software toolkit)

RRID:SCR_006525

Java toolset for working with next generation sequencing data in the BAM format.

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BWA (software resource)

RRID:SCR_010910

Software for aligning sequencing reads against large reference genome. Consists of three algorithms: BWA-backtrack, BWA-SW and BWA-MEM. First for sequence reads up to 100bp, and other two for longer sequences ranged from 70bp to 1Mbp.

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NOD.Cg-Prkdcscid Il2rg/SzJ (organism)

RRID:IMSR_JAX:005557

Mus musculus with name NOD.Cg-Prkdcscid Il2rg/SzJ from IMSR.

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SaOS-2 (cell line)

RRID:CVCL_0548

Cell line SaOS-2 is a Cancer cell line with a species of origin Homo sapiens (Human)

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A-549 (cell line)

RRID:CVCL_0023

Cell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)

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RD (cell line)

RRID:CVCL_1649

Cell line RD is a Cancer cell line with a species of origin Homo sapiens (Human)

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R Project for Statistical Computing (software resource)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

View all literature mentions