Medicine & Health

Publication Search Results

Now showing 1 - 1 of 1
  • (2021) Wooi, Danson
    Fusion genes are known to be key diagnostic, prognostic and therapeutic targets in blood cancers. However in sarcoma, the fusion gene landscape has yet to be fully elucidated due to the heterogeneity of fusion gene partners and rarity of the samples. Current fusion gene diagnostics are only able to detect presence of the fusion and are unable to identify novel fusion gene partners or splice isoforms. Therefore to expand on the knowledge of fusion genes in sarcoma, my study aims to sequence RNA from archived sarcoma patient samples by targeting a panel of 255 genes known to be involved in fusion. Through targeted sequencing, accurate fusion gene detection can be achieved along with information on novel fusion gene partners or splice junctions. Finally gene expression analysis was performed to gain insight into the transcriptome of sarcoma and identify the relationship of fusion genes to clinical prognostic markers. In this study, RNA was sourced from formalin fixed paraffin embedded (FFPE) samples, which is often degraded and chemically modified. However based on quality assessment, fusion gene detection could still be carried out in libraries as small as 1 million reads. Fusion genes were found to be identified in 44% (43/98) of patient samples with 38 of these fusions consistent with those reported in literature. Novel fusion isoforms were also found to contain different breakpoints but retain the same protein domains as the recurrent fusion isoform. Through gene expression analysis of fusion positive and negative Ewing’s sarcoma, it was found that 52% of differentially expressed protein coding isoforms contained fewer regulatory elements compared to the principal isoform of the gene. This suggests that presence of the fusion in Ewing’s sarcoma may be related to eased expression of certain genes. To identify any other links fusion genes may have to gene expression, levels of prognostic immune markers were compared to fusion type. While fusion type did not appear to be associated with expression of these immune genes, varying expression levels between samples may potentially act as a predictor for immunotherapy success.