Fusion genes in cancer

Cancer cells commonly have structurally altered chromosomes (translocations, insertions, deletions, and duplications), and this may give rise to fusion genes producing chimeric RNA molecules. Chimeric RNA may also be caused by mechanisms such as polymerase read-through and trans-splicing. Certain chimeric RNAs are specific to cancer cells, and are as such ideal as cancer biomarkers and drug targets.

The AKAP13-PDE8A fusion is recurrent in colorectal cancer (Nome et al., 2013)
The AKAP13-PDE8A fusion is recurrent in colorectal cancer (Nome et al., 2013)

The research group uses high-throughput sequencing of DNA and RNA to detect known and novel fusion genes in cancer. Several recurrent fusion transcripts have been discovered from testicular (Hoff et al., 2016), colorectal (Nome et al., 2013 and Nome and Hoff et al., 2014) and prostate cancers (Zhao et al., 2017, Paulo et al., 2012, and Barros-Silva et al., 2013).

The group has also developed various research tools for the detection and study of oncogenic fusion genes. The ScaR software is a bioinformatics tool for sensitive detection of fusion transcripts from RNA-seq data (Zhao et al., 2019), and chimeraviz is a software for visualization of fusion genes (Lågstad et al., 2017). A novel oligonucleotide microarray-based system for fusion gene detection was developed (Skotheim et al., 2009 and Løvf et al., 2011).

Selected papers
Zhao S*, Hoff AM*, and Skotheim RI (2020). ScaR - A tool for sensitive detection of known fusion transcripts: Establishing prevalence of fusions in testicular germ cell tumours. NAR Genomics and Bioinformatics 2(1): 1-12 *Equal contribution

Carm KT, Hoff AM, Bakken AC, Axcrona U, Axcrona K, Lothe RA, Skotheim RI*, and Løvf M (2019). The clinical usefulness of molecular classification of primary prostate cancer is challenged by interfocal heterogeneity. Scientific Reports 9: 13579 *Corresponding author

Lågstad S, Zhao S, Johannessen B, Hoff AM, Lingjærde OC, and Skotheim RI (2017). Chimeraviz: A Bioconductor package for visualizing chimeric RNA. Bioinformatics 33(18): 2954-2956

Hoff AM, Alagaratnam S, Zhao S, Bruun J, Andrews PW, Lothe RA, and Skotheim RI (2016). Identification of novel fusion genes in testicular germ cell tumors. Cancer Research 76(1): 108-16

Nome T, Thomassen GOS, Bruun J, Ahlquist TC, Bakken AC, Rognum T, Nesbakken A, Lorenz S, Sun J, Barros-Silva JD, Lind GE, Myklebost O, Teixeira MR, Meza-Zepeda LA, Lothe RA, and Skotheim RI (2013). Common fusion transcripts identified in colorectal cancer cell lines by high throughput RNA sequencing. Translational Oncology, 6(5):546-53

Barros-Silva JD, Paulo P, Bakken AC, Cerveira N, Løvf M, Henrique R, Jerónimo C, Lothe RA, Skotheim RI, and Teixeira MR (2013). Novel 5' fusion partners of ETV1 and ETV4 in prostate cancer. Neoplasia 15(7): 720-726

Paulo P, Barros-Silva JD, Ribeiro FR, Ramalho-Carvalho J, Jerónimo C, Henrique R, Lind GE, Skotheim RI, Lothe RA, and Teixeira MR (2012). FLI1 is a novel ETS transcription factor involved in gene fusions in prostate cancer. Genes Chromosomes. Cancer 51(3): 240-249

Løvf M*, Thomassen GOS*, Bakken AC, Celestino R, Fioretos T, Lind GE, Lothe RA, and Skotheim RI (2011). Fusion gene microarray reveals cancer type-specificity among fusion genes. Genes Chromosomes. Cancer 50: 348-357 *Equal contribution

Skotheim RI, Thomassen GOS, Eken M, Lind GE, Micci F, Ribeiro FR, Cerveira N, Teixeira MR, Heim S, Rognes T, and Lothe RA (2009). A universal assay for detection of oncogenic fusion transcripts by oligo microarray analysis. Molecular Cancer 8(1): 5


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