Molecular profiling of common fragile sites in human fibroblasts

Abstract

Common fragile sites (CFSs) can drive genomic instability. The basis for their fragile nature is not clear, but lymphocyte CFSs have been mapped to regions with low replication initiation events and late replication completion. These features are now used to rapidly identify CFSs in different fibroblast cells. Common fragile sites have been mapped primarily in lymphocytes, but recent analyses show that the setting of these sites relies on cell type–dependent replication programs. Using a new approach, we molecularly mapped common fragile sites in human fibroblasts and showed that commitment to fragility depends on similar replication features in fibroblasts and lymphocytes, although different loci are committed in each cell type. Notably, the common fragile sites that we identified overlapped heretofore unexplained deletion clusters observed in tumors.