Andreas Midbøe Hoff, who recently defended his PhD thesis, has together with colleagues at Department of Molecular Oncology discovered novel fusion genes in testicular germ cell tumours. The results are published in the current issue of Cancer Research (journal impact factor 9.28)
Altogether eight novel fusion transcripts and one gene with alternative promoter usage, ETV6, were discovered by a high-throughput RNA-sequencing approach. Four of the fusion genes were recurrently expressed in an extended set of testicular cancers, but not found from any normal tissues or embryonic stem cells included as non-cancer pluripotent controls. The fusion genes RCC1-HENMT1 and RCC1-ABHD12B were highly expressed in testicular cancers with poorly differentiated histological subtypes (seminomas and embryonal carcinomas). Absent expression from cancers with more differentiated histological subtypes (such as teratomas), as well as observations from an in vitro differentiation assay, demonstrated that the fusions are markers of pluripotency in a malignant setting. These are the first fusion genes described in testicular cancer, and may serve as genomic biomarkers of malignant progression.
This was the third out of three papers in Hoff's PhD thesis, "Identification of novel fusion genes and transcript variants in cancer". On November 23rd, Hoff successfully defended this thesis for the Philosophiae Doctor (PhD) degree at the University of Oslo. As opponents were three expert researchers in cancer genomics, Kristian Almstrup from Copenhagen, Stian Knappskog from Bergen, and Vessela Kristensen from Oslo. Earlier the same day, Hoff presented his trial lecture over the given topic "Mechanisms of nucleosome and chromatin dynamics".
The paper was included in Hoff’s PHD thesis, together with two additional papers where applications of high-throughput sequencing of DNA and RNA have been utilized to identify fusion transcripts and transcript variants relevant to development of colorectal cancer and testicular germ cell tumors:
Hoff’s thesis included three papers where applications of high-throughput sequencing of DNA and RNA have been utilized to identify fusion transcripts and transcript variants relevant to development of colorectal cancer and testicular germ cell tumors:
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): 108-116
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, and Skotheim RI (2014). High frequency of fusion transcripts involving TCF7L2 in colorectal cancers: Novel fusion partner and splice variants. PLOS ONE 9(3): e91264 *Equal contribution
Genome Biology Group
Department of Molecular Oncology
Dissertation announcement at the University of Oslo