Transcriptomics

Dataset Information

97

RNA Sequencing Quantitative Analysis of cell lines derived from tumours from two mouse models of human osteosarcoma that recapitulate clinically distinct human osteosarcoma subtypes.


ABSTRACT: Purpose: Osteosarcoma (OS) is the most common primary bone malignancy. OS consists of several subtypes including fibroblastic, osteoblastic and chondroblastic OS. We have developed genetically engineered mouse models of human OS that recapitulate two distinct subtypes, fibroblastic (Osx-CreLox p53-/- Rb-/-) and osteoblastic (Osx-Cre shRNA p53-/-) OS. The goal of this study was to identify transcriptional differences that distinguish the two subtypes. Methods: mRNA profiles of cell lines derived from tumours from Osx-Cre p53fl/fl Rbfl/fl (fibroblastic OS) and Osx-Cre shRNA TRE-p53.1224 pRbfl/fl (osteoblastic OS) mouse models were generated by RNA sequencing, in triplicate, using Illumina HiSeq2000. The sequence reads that passed quality filters were analyzed at the transcript level with TopHat followed by Cufflinks. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 12,436 transcripts in the tumours of Osx-Cre p53fl/fl Rbfl/fl and 12,074 Osx-Cre shRNA TRE-p53.1224 pRbfl/fl with the TopHat workflow. RNA-seq data confirmed stable expression of 25 known housekeeping genes. Conclusions: Our study represents a detailed analysis of OS subtype transcriptomes generated by RNA-seq technology. mRNA profiles of cell lines derived from tumours from two genetically engineered mouse models of human osteosarcoma (Osx-Cre p53fl/fl Rbfl/fl and Osx-Cre shRNA TRE-p53.1224 pRbfl/fl) were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000.

ORGANISM(S): Mus musculus  

SUBMITTER: Emma K Baker  Alistair M Chalk   Alistair Morgan Chalk   Carl R Walkley    

PROVIDER: E-GEOD-58916 | ArrayExpress| 2015-08-19

SECONDARY ACCESSION(S): SRP043671GSE58916PRJNA253921

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

BET inhibitors induce apoptosis through a MYC independent mechanism and synergise with CDK inhibitors to kill osteosarcoma cells.

Baker Emma K EK   Taylor Scott S   Gupte Ankita A   Sharp Phillip P PP   Walia Mannu M   Walsh Nicole C NC   Zannettino Andrew C W AC   Chalk Alistair M AM   Burns Christopher J CJ   Walkley Carl R CR  

Scientific reports 20150506


Osteosarcoma (OS) survival rates have plateaued in part due to a lack of new therapeutic options. Here we demonstrate that bromodomain inhibitors (BETi), JQ1, I-BET151, I-BET762, exert potent anti-tumour activity against primary and established OS cell lines, mediated by inhibition of BRD4. Strikingly, unlike previous observations in long-term established human OS cell lines, the antiproliferative activity of JQ1 in primary OS cells was driven by the induction of apoptosis, not cell cycle arrest  ...[more]

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