Chromosomal fragile sites in the context of nuclear achitecture
Chromosomal fragile sites (CFSs) are genomic regions prone to form gaps or breaks on metaphase chromosomes. As CFSs often appear as hot spots for gross chromosomal rearrangements in cancer cells, it is of high clinical relevance to map CFSs genome-wide for better understanding of complex aberrant karyotypes and to predict their clinical prognosis. I established a new approach to map CFSs genome-wide. This mapping method enables an unbiased analysis of chromosomal instability as it is not relying on conventional cytogenetic analysis, using by eye-defined structures to classify broken chromosomes on metaphase spreads. Instead, using a FANCD2 ChIP-seq (Chromatin Immunoprecipitation followed by massively parallel sequencing) high-throughput approach opens the way for a standardized mapping of CFSs genome-wide. The aim of this research project funded within the IMPULSEproject programme is to expand the view on CFSs focusing on aspects of nuclear localization of CFSs to identify the connection between the fragility of certain genomic regions and cancer predisposing and premature aging related disorders.