Sendurai Mani, Associate Director of Translational Oncology at the Legorreta Cancer Center, is presenting a series exploring some of the most influential scientific papers that have shaped the field of cancer research.
Paper 1: The Origins of Proto-Oncogenes
“I recently shared an AI-generated (Claude) list of the top 200 papers that have shaped cancer research.
Starting today, I’ll highlight one paper each day, beginning with N1.
What if some of cancer’s most dangerous genes are not foreign invaders, but normal genes operating in the wrong context?
In 1976, Dominique Stéhelin, Harold Varmus, J. Michael Bishop, and Peter Vogt showed that DNA sequences related to the transforming gene of avian sarcoma viruses were also present in normal bird cells.
This finding was a foundational shift in cancer biology. It helped establish the proto-oncogene concept: viruses can capture and alter normal cellular genes, turning them into oncogenes that drive cancer. The viral gene later became known as v-src; its normal cellular counterpart, c-src, is a proto-oncogene.
The lesson remains strikingly relevant today: cancer often arises not from wholly foreign biology, but from normal growth-control machinery that has been rewired, deregulated, or activated at the wrong time.
This insight opened the path to identifying cancer genes – and ultimately to developing therapies that target their vulnerabilities.”
Title: DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA
Authors: Dominique Stéhelin, Harold E. Varmus, J. Michael Bishop, Peter K. Vogt
