Neoplastic cells typically possess numerous genomic lesions, which may incl
ude sequence alterations (point mutations, small deletions, and insertions)
and/or gross structural abnormalities in one or more chromosomes (large-sc
ale deletions, rearrangements, gene amplifications). Based upon this genera
l observation, it has been suggested that cancer cells are genetically unst
able, and that acquisition of genomic instability may represent an early st
ep in the process of carcinogenesis and a general feature of many human tum
ors. Numerous studies have appeared that characterize the nature and freque
ncy of occurrence of various molecular lesions in human tumors, and signifi
cant progress has been made towards the elucidation of the molecular mechan
isms that govern genetic stability in normal cells and genetic instability
in neoplastic cells. In this review, we examine the evidence that genomic i
nstability plays a significant role in the genesis of various human tumors.
Furthermore, we consider the possible molecular pathways to tumorigenesis
in humans and how different forms of genetic instability may impact upon th
ese pathways.