Two new academic degrees digitally defended at University of Oslo, by members of the K. G. Jebsen Colorectal Cancer Research Centre
In June, Tuva Høst Brunsell (MD) defended her PhD "Heterogeneity of prognostic biomarkers in colorectal liver metastases", Institute for Clinical Medicine, Faculty of Medicine, University of Oslo. The thesis includes three papers (Brunsell et al., Clin Colorectal Cancer 2020; Brunsell et al., Eur J Surg Oncol 2019; Berg*, Brunsell* et al., submitted). On September the 4th, Christer Anker Andreassen, defended his MSc, Institute of Biosciences, Faculty of Mathematics and Natural Sciences, University of Oslo. "The functional and clinical impact of the E3 Ubiquitin ligase NEDD4 in colorectal cancer and its role in regulating PTEN and P53".
Brunsell reports high concordance of clinically relevant gene mutations among multiple liver metastases in individual patients, and for the first time shows heterogenous radiological responses to neoadjuvant therapy among 10% of patients undergoing resection of colorectal cancer liver metastases, which was associated with poor outcome.
She demonstrated co-mutational patterns as a strong negative prognostic feature, but even within this group heterogeneity of genome wide copy number aberrations identifies a smaller subgroup with particular inferior outcome. The lab work was conducted at Dept Molecular Oncology, Institute for Cancer Research, and the clinical work in Dept Gastrointestinal cancer, with Prof.s Arild Nesbakken as main supervisor and prof Lothe as co-supervisor. Brunsell was instrumental in the initial phase of the SMART-CRC research project, and her thesis build on this biobank and strategic approaches. The project now includes > 2500 samples from > 500 first time resected colorectal liver metastatic patients, and genomic and pharmacological studies on tumor heterogeneity and drug sensitivities ongoing in the multidisciplinary research program. Tuva continues as postdoc.
In his MSc work, Christer Anker Andreassen demonstrates that knock-down of NEDD4 in colorectal cancer cells leads to changes in growth pattern and drug sensitivity independent of the NEDD4 ligase function to degradation of PTEN and P53. Finally, the study concludes on the prognostic value pf PTEN in primary colorectal cancer, an issue debated in the literature. Christer obtained top level evaluation and continues as research assistant, he was supervised by senior scientist at Dept Mol Oncol, Dr. Jarle Bruun (main supervisor) and Dr. Edward Leithe.