Cell Cycle Checkpoints, Genomic Integrity, and Cancer

Cancer cells typically exhibit a large number of phenotypic differences from normal cells, including loss of contact inhibition, changes in adhesion, loss of gap junctions, loss of differentiation characteristics, decreased proteolysis, increased invasiveness, angiogenesis, metastasis, restoration of telomerase, decreased apoptosis, and decreased drug sensitivity. Underlying these phenotypic changes must be a large number of genomic changes. How do such massive changes in the genome occur? In 1976, Peter Nowell suggested that an early change in precancerous cells may be a mutation that creates genomic instability (Nowell 1976). This prediction is being borne out.