Disruption of oncogene/tumor suppressor networks during human carcinogenesis.

Oncogenes were initially discovered as retrovirally transmitted tumor causing agents. The realization that such retroviral oncogenes constitute specifically altered versions of cellular genes-proto-oncogenes, was a landmark discovery that set the stage for the molecular and mechanistic era of cancer research. Moreover, the studies on oncogene functions have been instrumental in delineating many of the paradigms of cellular signal transduction. In contrast to the original studies in animals, oncogenic activation through retroviral transmission does not appear to be a major factor in human tumorigenesis. However, oncogenes are frequently activated by gain of function mutations or fusions with other genes, or they are aberrantly expressed due to amplification, increased promoter activity, or protein stabilization, and hence they play integral roles in the genesis of human tumors.