Selected highlights from 2021 at Dept Molecular Oncology

2021 was another year marked by frequent home office and reduced lab activity due to covid-19 restrictions, but our employees managed to keep up with the main research activities. We published or co-authored 20 papers registered in PubMed, including two papers in Genome Med, two in Nat Commun and one in Hepatology. Selected highlights from our major national and international collaborations follow:

Project group leaders Anita Sveen and Bjarne Johannessen published a major work from The Norwegian Cancer Genomics Consortium, presenting the ”expressed mutation dose” as a determinant of the functional consequences of mutations in colorectal cancer (Sveen et al., Genome Med 2021). In this study, whole-exome and RNA sequencing of tumours were integrated at allele-specific resolution to show that the majority of somatic cancer mutations were not expressed. However, mutation expression levels varied according to the target gene and mutation type, and correlated with downstream oncogenic signatures. Proof-of-concept for a therapeutic relevance was shown by associations between expression levels of mutated alleles and sensitivity to targeted anti-cancer agents in cell lines and patient derived tumor organoids.

PhD student Seyed Hossein Moosavi was first author on a multidisciplinary team effort of the recent K.G.Jebsen Colorectal Cancer Research Centre, identifying a novel gene expression-based subtyping framework for metastatic colorectal cancer (Moosavi et al., Genome Med 2021). Each of the five new and biologically distinct liver metastasis subtypes originated from different progenitor cell types, and a subtype expressing biological features of cancer aggressiveness was also an independent predictor of a poor patient survival. In a parallel innovation project we aim to develop the subtypes into a framework for biology-guided treatment of metastatic colorectal cancers (A patent application was filed in 2021 with Sveen as primary inventor).

Researcher Hege Marie Vedeld in the Lind group analyzed epigenetic markers in bile (liquid biopsy) from patients with primary sclerosing cholangitis (PSC) and achieved accurate detection of cholangiocarcinoma up to 12 months prior to cancer diagnosis; this was a collaborative study with the Norwegian PSC Center, OUS- Rikshospitalet (Vedeld et al., Hepatology Dec 2021 ahead of print). This liquid biopsy test has potential as a screening method for early detection of cholangiocarcinoma in patients with PSC.

A study from the global TEsticular CAncer Consortium (TECAC), led by Katherine L. Nathanson, U of Pennsylvenia, revealed 22 novel genetic risk loci for testicular germ cell tumor by analyses of more than 10 000 cases (including 660 Norwegian cases from our dept) and approximately 180 000 controls (Pluta J et al., Nat Commun. 2021). The results explain more than forty percent of heritability for development of testicular cancer, and men with a high polygenic risk score had seven fold increased disease risk compared to men with median score (for more: see news release PennMedicine: https://www.pennmedicine.org/news/news-releases/2021/july/penn-led-consortium-identifies-more-genetic-markers-for-inherited-testicular-cancer).

Four academic degrees were completed. One MSc and one MD defended their PhDs at the Institutes for Clinical Medicine, Universities of Oslo and Bergen, respectively. Kristina Totland Carm successfully defended her thesis “Genomic aberrations and molecular subtypes in multifocal prostate cancer” with group leader Skotheim as the main supervisor. Carm continues her research career as a post doc in a collaborative project on ovarian cancer at the Institute. Kristine Øvreås Aasebø conducted parts of her studies in the Lothe lab and defended her thesis “Presence and effect of tumour biomarkers in a population-based series of metastatic colorectal cancer patients” under the main supervision of Halfdan Sørbye at Haukeland University Hospital, Bergen. Aasebø is pursuing medical specialist training in oncology. Two students completed their MSc degrees at Dept Biosciences, University of Oslo, and at University of Milan (ERASMUS exchange student), Italy, under the supervision of Edward Leithe and Skotheim, respectively.

Professor Ragnhild A. Lothe received the “Excellent Researcher Award” from Oslo University Hospital and Assoc. professor Anita Sveen received the Ragnar Mørks legacy prize for 2021.

Lothe was member of the scientific programme committee of the EACR-OECI joint conference on “Molecular pathology approach to cancer”, held March 23-24, 2021.

More than 75% of our budget is dependent on external grants, and we are grateful to all our funding sources. This year we received new grants from the Norwegian Cancer Society (to Marine Jeanmougin and Lothe) and an innovation grant to Sveen from U of Oslo.

 
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