The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Digital Trial Lecture - time and place
Adjudication committee
- First opponent: Professor Torsten O. Nielsen, University of British Columbia, Canada
- Second opponent: Senior scientist Nick Tobin, Karolinska Institutet, Stockholm, Sweden
- Third member and chair of the evaluation committee: Associate Professor Kristina Lindemann, Institute of Clinical Medicine, University of Oslo
Chair of defence
Associate Professor Manuela Zucknick, Institute of Basic Medical Sciences, University of Oslo
Principal Supervisor
Professor II Therese Sørlie, Institute of Clinical Medicine, University of Oslo
Summary
Over ten million people are diagnosed with cancer every year. Each tumor that is detected is unique. In his dissertation On the genetic determinants of cancer phenotypes, Christian Fougner and colleagues have investigated the origin of this variation, and analyzed how tumors can be classified in biologically and clinically meaningful ways. The work focuses on breast cancer, but also includes analyses carried out across more than twenty types of cancer.
Breast cancer can be divided into subtypes. One of these, claudin-low, shows unusually large variation within the subtype. Through genomic and transcriptomic analyses of human and murine mammary tumors, Fougner with colleagues, finds an explanation for this phenomenon: Claudin-low is not truly a subtype, but rather a set of properties that can arise on top of an underlying subtype. Thus, a group of breast tumors have previously been classified in a misleading way that obscures clinically relevant characteristics. The findings also suggest that the immune system is often suppressed from attacking these tumors, and that this could be explored as a treatment target.
The characteristics of tumors are largely determined by changes to their genome and epigenome. For example, a gene can be copied or deleted (copy number aberration), or it can be methylated (thereby modulating its transcription). To understand how subtypes such as claudin-low arise, Fougner and colleagues analyzed the relationship between copy number, methylation, and gene expression across 23 cancer types, and in over ten thousand genes. The results suggest that copy number changes function as a central driver of inter-tumor heterogeneity, while the majority of expression-methylation correlations found in cancer might be a reflection of cell-of-origin and normal cell admixture. A web-based tool was developed to enable customizable analyzes of transcriptional associations to methylation and copy number aberrations.
The findings in this dissertation affect the way we understand the genetic origins of heterogeneity in cancer, and contributes new tools and data sets that can be leveraged in future studies.
Additional information
contact the Research Support staff