Large scale genomic instability

Centre for Cancer Biomedicine (CCB) is among the most succesful Norwegian Centre of Excellence. CCB’s vision, during the ten year period from 2007 - 2017, was to “unite basic and translational cancer research for the benefit of the patient”.

CCB remained faithful to this vision, and delivered top-level multidisciplinary research results from which innovations emerged and clinical studies and trials were initiated.

Through CCB the institute for Cencer Genetics and Informatics was given access to valuable collaborations with the clinic and with a larger scientific community. Being a part of CCB undoubtedly helped put the institute in a position where it was able to expand, and thereby provided the possibility, among others, to perform patient analysis on a much larger scale. This in turn made the institute leading in its field.

Achievements for Håvard Danielsen's group in CCB

Cancer is a disease characterized by heterogeneity and genomic instability. The research group has been developing high throughput methods for detection and characterization of large-scale genomic instability (chromatin structure and DNA ploidy), based on high-resolution digital microscopy and advanced image analysis (Danielsen et al. Nature Reviews Clinical Oncology, 2016; Nielsen et al. Critical Reviews in Oncogenesis, 2008).

The group included an interdisciplinary team of members with background in medicine, biology, mathematics and computer science. We have been studying archival material from the time of diagnosis from cancer patients with proper clinical follow-up and known prognosis. Several methods such as IHC, FISH, DNA Ploidy, Tissue Micro Array, as well as original methods developed in the group (Nucleotyping, 3D-reconstruction, ImmunpPath and MicroTracker) are used in an attempt to reveal and understand the 3-dimentional organisation of chromatin, and how this organisation controls gene expression (Nielsen et al. Cytometry, 2012; Nielsen et al. Annals of Cellular Pathology, 2012).

The group has been engaged in the search for new diagnostic and prognostic markers among these methods and results, and have been running clinical validation studies on large series of colorectal (Hveem et al. British Journal of Cancer, 2014), oesophageal (Dunn et al. British Journal of Cancer, 2011), prostate (Cyll et al. British Journal of Cancer, 2017; Hveem et al. British Journal of Cancer, 2016; Silva et al. Translational Oncology, 2016; Pretorious et al. Cellular Oncology, 2009) and gynaecological cancers (Hveem et al. Cancer Epidemiology, Biomarkers & Prevention, 2017; Nielsen et al. Cytometry, 2015; Micci et al. Genes, Chromosomes & Cancer, 2013; Pradhan et al. International Journal of Gynecological Pathology, 2010; Kildal et al. Annals of Oncology, 2009; Kildal et al. European Journal of Cancer, 2009; Micci et al. Virchows Archive, European Journal of Pathology, 2008) with a minimum of 5, and up to 20, years of clinical follow-up, with emphasis on disease-free survival.

The aim has all along been to improve cancer treatment by the identification of better prediction and prognosis of the outcome among these patients. Several of the abovementioned papers have been collaborations with other CCB members, and contributions with biological knowledge, clinical data, and statistical analysis in particular, has beencrucial to the success of these studies.

Our focus post CCB

In 2016, the institute was awarded a large Lighthouse grant from the Norwegian Research Council for our DoMore! project.

The DoMore! project spanned 5 years (2016-2021) and the main focus was to radically improve prognostication and hence treatment of cancer by introducing in silico pathology. Close collaborations with some of the CCB members continued in the DoMore! project.

 
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