Testicular germ cell tumour

Testicular germ cell tumour (TGCT) is the most common type of cancer among young men (15 to 45 years of age).

Testicular tumourigenesis mimics the early embryogenesis
Testicular tumourigenesis mimics the early embryogenesis
Embryonal carcinoma (EC) cells, found in certain testicular germ cell tumours (TGCTs), represent a striking paradigm for malignant cells with stemness properties. Their pluripotent state allows them to self-renew, as well as differentiate, to give a disorganized array of cell and tissue types. EC cells are morphologically similar to embryonic stem (ES) cells, and the two also share cell surface markers and overall gene expression programmes.

Overall, this imply that ES cells can be considered the non-malignant counterpart of EC cells, providing the rare situation where the "normal" counterpart of a cancer cell with stemness properties is readily accessible, and can be observed through its progression to the malignant state.

By comparing gene expression of EC and ES cells across the genome at high resolution, we aim to gain insight into the role of stem cells in the development and progression of TGCTs, in particular, and cancer in general.

The research project is run jointly between the Molecular Genetics Group and the Genome Biology Group. We have published review articles about the TGCT genome, TGCT epigenome, as well as the TGCT transcriptome.

Selected original publications
Rajpert-De Meyts E and Skotheim RI (2018). Complex polygenic nature of testicular germ cell cancer suggests multifactorial aetiology. Eur. Urol. 73(6): 832-833

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 Res. 76(1): 108-116

Brabrand S*, Johannessen B*, Axcrona U, Kraggerud SM, Berg KG, Bakken AC, Bruun J, Fosså SD, Lothe RA, Lehne G, and Skotheim RI (2015). Exome sequencing of bilateral testicular germ cell tumors suggests independent development lineages. Neoplasia 17(2): 167-174 *Equal contribution

Chung CC*, Kanetsky PA*, Wang Z*, Hildebrandt MAT*, Koster R*, Skotheim RI*, Kratz CP*, Turnbull C*, Cortessis VK*, [21 additional authors including Bakken AC, Kraggerud SM, Lothe RA], Chanock SJ, and Nathanson KL (2013). Meta-analysis identifies four new loci associated with testicular germ cell tumor. Nat. Genet. 45(6): 680-685 *Equal contribution between nine authors

Alagaratnam S, Harrison NJ, Bakken AC, Hoff AM, Jones M, Sveen A, Moore H, Andrews PW, Lothe RA, and Skotheim RI (2013). Transforming pluripotency: an exon-level study of malignancy-specific transcripts in human embryonal carcinoma and embryonic stem cells. Stem Cells Dev. 22(7): 1136-1146

Skotheim RI, Lind GE, Monni O, Nesland JM, Abeler VM, Fosså SD, Duale N, Brunborg G, Kallioniemi O-P, Andrews PW, and Lothe RA (2005). Differentiation of human embryonal carcinomas, in vitro and in vivo, reveals expression profiles relevant to normal development. Cancer Res. 65(13): 5588-5598

 
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