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MA23 - Preclinical Models and Genetics of Malignant Pleural Mesothelioma (ID 353)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Mesothelioma
- Presentations: 1
- Now Available
- Moderators:Ramon Palmero Sánchez, Raphael Bueno
- Coordinates: 9/10/2019, 14:30 - 16:00, Copenhagen (1980)
MA23.09 - Fusion Genes Identified from Whole Genome and Whole Transcriptome Sequencing of Malignant Pleural Mesothelioma Tumours (Now Available) (ID 2014)
14:30 - 16:00 | Author(s): Harald Oey
Malignant Pleural Mesothelioma (MPM) is an asbestos-related cancer without curative treatment. Fusion genes result from structural chromosomal rearrangements such as translocation, inversion, amplification and deletions, leading to erroneous apposition of components of two or more genes. Consequences include abolition of gene functions that protect against tumourigenesis, or increased activation of genes that promote cell proliferation. To identify fusion genes in MPM genomes, we executed whole genome sequencing (WGS) on eight MPM tumours, and validated the expression of putative fusion genes identified from WGS by whole transcriptome analysis (RNA-Seq).Method
Histology of eight MPM tumours was confirmed by two qualified anatomical pathologists, prior to extraction of genomic DNA and RNA. Whole genome and whole transcriptome sequencing were performed using Illumina HiSeq platforms. Following stringent data processing and filtration, putative fusion variants were called using an in-house bioinformatics pipeline. Fusion events with potential functional consequences were then validated by whole transcriptome analysis, and annotated using TCGA Fusion Gene Data Portal and The Gene Ontology Resource.Result
A total of 592 and 321 putative fusion variants were called respectively from WGS data using Delly, and from RNA-Seq using STAR-Fusion computational tools. Expression of WGS putative fusion variants was confirmed in RNA-Seq data, resulting in twelve fusion genes being identified. Among 24 genes involved in fusion events, twenty-two were listed in TCGA Fusion Gene Data Portal with gene partners that were not identified in our cases. Two genes were novel to that database. Multiple functional processes that may lead to tumour development were attributable to these genes including protein polyubiquitination, protein deubiquitination, antioxidant activity, DNA repair, immune response, integrin-mediated signalling pathway, chromatin organization, transcription coactivator activity, angiogenesis, natural killer cell proliferation and DNA-binding transcription factor activity.Conclusion
In combination, WGS and RNA-Seq data analysis revealed several fusion genes that warrant further investigation as possible drivers of malignant mesothelioma, and which may serve as diagnostic and therapeutic targets.
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