13 Oncogenes and Clinical Cancer

Abstract

I. INTRODUCTION
Although observations on human cancer provided the earliest hints that genetic damage might underlie tumorigenesis (see Chapter 1), the first experimental access to genes that can cause cancer was gained with tumor viruses of birds and animals, and for some years, there was no assurance that these experimental models would provide insight into the genesis of human disease. Discovery of the proto-oncogenes from which retroviral oncogenes arise made the mechanisms of viral tumorigenesis germane to human cancer and brought new questions to the fore. Might proto-oncogenes be damaged in human cancer cells, and if so, how might damage to these genes contribute to neoplastic growth? Answers have been sought primarily through two lines of enquiry: pursuit of the karyotypic abnormalities found in many human cancers and the use of functional assays to search for oncogenes in the DNA of human tumors. The provisional answers now in hand sustain the view that genetic damage is an important vehicle of tumorigenesis, demonstrate how some of the proto-oncogenes can be important targets for that damage, and in the long term, promise new approaches to the diagnosis and management of human cancer.

II. CHROMOSOMAL TRANSLOCATIONS AND INVERSIONS
In 1914, T. Boveri proposed that abnormalities of chromosomes might be a cause of cancer (Boveri 1929). More than 60 years passed before the prescience of Boveri’s suggestion became evident. Now we know that human cancer cells can display a rich diversity of chromosomal abnormalities, and that at least some of these abnormalities are indeed...