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See Inside May 2007

Chromosomal Chaos and Cancer

Current wisdom on the role of genes in malignancy may not explain some features of cancer, but stepping back to look at the bigger picture inside cells reveals a view that just might

When I first began to study cancer as a young postdoctoral fellow in the early 1960s, it looked to leading scientists as though viruses could be the cause of most, if not all, malignancies. That idea was based on the discovery of several tumor- and leukemia-producing viruses that could infect a host cell and insert their own genetic material into its genome, sparking a cancerous transformation and proliferation of the cell. I was optimistic and naive enough to hope that if researchers could understand the exact molecular mechanisms by which such viruses caused cancer, we could develop vaccines to eliminate one of humanity's most dreaded diseases.

My own contribution to that pursuit came in 1970, when my colleagues, Michael Lai and Peter Vogt, and I managed to isolate a specific gene, src, which was suspected to be the tumor-initiating culprit in avian Rous sarcoma virus. Within a few years, more creative scientific minds than mine had followed this lead to a realization that a closely related gene was already present in the normal DNA of animals, including humans. And a new cancer model was born: it proposed that some triggering event, such as a mutation in a human cell's own version of src, could ignite tumorigenic powers like those possessed by its viral counterpart. The cancer-promoting potential of such a time bomb buried in our personal genomes earned it the title of "proto-oncogene." Once the mutation occurred, it would become a full-fledged oncogene.

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