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 research group uses high-throughput sequencing of RNA and DNA 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 research group has developed a novel oligonucleotide microarray-based system for fusion gene detection (references below). This tool enables screening of a sample for the presence of all oncogenic fusion transcripts known to date in a single experiment.

Selected papers
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

Hoff AM*, Johannessen B*, Alagaratnam S, Zhao S, Nome T, Løvf M, Bakken AC, Hektoen M, Sveen A, Lothe RA, and Skotheim RI (2015). Novel RNA-variants expressed by subsets of colorectal cancer. Oncotarget 6(34): 36587-36602 *Equal contribution

Nome T, Hoff AM, Bakken AC, Rognum TO, Nesbakken A, Skotheim RI (2014). High frequency of fusion transcripts involving TCF7L2 in colorectal cancer: novel fusion partner and splice variants. PLoS One 9(3), e91264

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

Løvf M*, Thomassen GOS*, Mertens F, Cerveira N, Teixeira MR, Lothe RA, and Skotheim RI (2013). Assessment of fusion gene status in sarcomas using a custom made fusion gene microarray. PLOS ONE 8(8): e70649 *Equal contribution

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

Celestino R, Sigstad E, Løvf M, Thomassen GOS, Grøholt KK, Jørgensen LH, Berner Å, Castro P, Lothe RA, Bjøro T, Sobrinho-Simões M, Soares P, and Skotheim RI (2012). Survey of 548 oncogenic fusion transcripts in thyroid tumours supports the importance of the already established thyroid fusions. Genes Chromosomes and Cancer 51(12): 1154-1164

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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