Large scale genomic instability
Genomic instability is a driving force in cancer. We study large-scale genomic instability by detecting aberrations and changes in chromosomes, chromatin organization and DNA ploidy.
Almost two meters of DNA is packed into each and every cell nucleus in the human body. It is tightly-packed and organized inside the nucleus in a manner that allows for both gene regulation and expression. This remarkable feat is accomplished by the meticulous wrapping of DNA around histone proteins in repeating units of nucleosomes to form the structure known as chromatin.
The identity and function of each cell in a multicellular organism is determined by the unique gene expression patterns of that cell type. These patterns are to a large extent determined by epigenetic mechanisms which do not involve changes in DNA sequence, but are still memorized and passed on to daughter cells. These epigenetic alterations in the pattern of DNA and histone modifications play a crucial role in cancer development.
The alterations can be chemically detected and measured (e.g. DNA methylation, histone modifications, microRNAs) or recognized and measured indirectly by studying the alterations in chromatin structure. This can be done on tissue sections from pathology archives, a necessity for obtaining sufficiently long follow-up time. In such retrospective studies of material from patients with a sufficient clinical follow-up, the results can easily be related to a number of established methods as well as directly to the final diagnosis and prognosis of each patient.
Our working hypothesis is that genomic instability is a driving force in cancer. High throughput methods are developed and used for detection and characterization of chromatin structure, gene expression and ploidy, based on high-resolution digital microscopy and advanced image analysis. Several methods such as DNA ploidy, IHC, FISH, CISH, Tissue Microarray, NanoString, as well as original methods developed at our institute (Nucleotyping, 3D-reconstruction, ImmunoPath and MicroTracker) are used in an attempt to reveal and understand the three-dimensional organization of chromatin, and how this organization controls gene expression.
We are also engaged in the search for new diagnostic and prognostic markers among these methods and results, and are running clinical validation studies on large series of colorectal, prostate and gynecological cancers with a minimum of 5, and up to 20, years of clinical follow-up, with emphasis on disease-free survival. We aim to improve cancer treatment through the identification of better prognostic markers for these groups of cancer patients.
This text was last modified: 16.09.2021