Large Scale Genomic Instability
Contents
Cell division, growth and differentiation are regulated by specific protein and DNA complexes in the cell nucleus. Though the basic structural organization of DNA and histons into nucleosomes and chromatin fibers are well known, little is known about the higher organization of chromatin and chromatin fibers.
Overview
Large scale genomic instability studies cell division, growth and differentiation are regulated by specific protein and DNA complexes in the cell nucleus. Though the basic structural organization of DNA and histons into nucleosomes and chromatin fibers are well known, little is known about the higher organization of chromatin and chromatin fibers. Still the pathologists can identify several differences in chromatin structure, looking at cancer tissue in the microscope. Nuclei atypia is traditionally one of the most important parameters for diagnostics and prognostification.
Large scale genomic instability
Chromosome instability is observed in a large number of cancer types. To which extent these changes are a cause or a consequence of cancer is still debated, but there is little doubt that further tumour development follows chromosome instability. Large chromosomal changes will influence chromatin structure as well as separate genes. Quantitative genomic alterations measured by DNA ploidy analysis are commonly observed in cancer. Aneuploidy is a typical sign of malignancy, and is often related to a poorer prognosis for the patient.
Our Research
Our hypothesis is that genomic instability is a driving force in cancer development and we are therefore focused on developing and establishing methods for analyzing genomic instability under cancer development. Principally, we have developed methods for measurement of what we call large scale genomic instability, in other words, we do not look at each gene per se but each nuclei, and study how the nuclei’s DNA content and chromatin structure is described (and understood) in each cancer biopsy related to the patient’s diagnosis and disease history.
Over the past ten years, we have developed and established new methods for investigating DNA organization and chromatin structure – methods which provide both quantitative and qualitative measurements for functional genetic changes under cancer development. The methods are based on computer-assisted image analysis where we transfer images of cells and tissues from a microscope (light-, laser scan-, and electron microscopy) to a computer. In the computer, we can digitize the images and analyze the chromatin’s structure and organization bit for bit. We call these investigations of interphase nuclei, nucleotyping.