The aberrant upregulation of FOXM1 serves as a 'first hit' where cells acquire genomic instability which in turn predisposes cells to a 'second hit' whereby DNA-damage checkpoint response (eg. inactivation of p53 or p16 or other TSGs) is abolished to allow damaged cells to proliferate and accumulate genetic aberrations/mutations required for cancer initiation. Here, CDKN2A is linked to cancer.