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A History of Cancer Research: Retroviral Insertional Mutagenesis

Joseph Lipsick1

  • 1Departments of Pathology, Genetics, and Biology, Stanford University, Stanford, California 94305-5324, USA lipsick@stanford.edu.

Cold Spring Harbor Perspectives in Biology
|July 5, 2023
PubMed

Insights

Retroviruses can cause cancer through insertional mutagenesis, where viral DNA activates cellular proto-oncogenes. This discovery revealed new oncogenes and tumor suppressors, impacting early gene therapy research.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • Early cancer research identified oncogenes in some retroviruses promoting tumorigenesis.
  • The mechanism by which oncogene-free retroviruses cause cancer remained unclear.
  • Proto-oncogenes are cellular genes that can promote cancer when aberrantly expressed.

Purpose of the Study:

  • To review the historical discoveries of retroviral insertional mutagenesis in cancer.
  • To explain how viral sequences can activate endogenous proto-oncogenes.
  • To discuss the implications for identifying new oncogenes, tumor suppressors, and gene therapy.

Main Methods:

  • Historical review of scientific literature from the 1980s.
  • Analysis of studies on retroviral mechanisms in cancer development.
  • Examination of the impact on oncogene and tumor suppressor gene discovery.

Main Results:

  • Discovery of insertional mutagenesis as a cancer-causing mechanism for oncogene-free retroviruses.
  • Viral sequences were found to drive aberrant expression of cellular proto-oncogenes.
  • Identification of novel oncogenes and tumor suppressor genes resulted from these studies.

Conclusions:

  • Insertional mutagenesis by retroviruses is a significant mechanism in cancer development.
  • This phenomenon expanded the understanding of oncogenesis and tumor suppression.
  • The findings highlighted risks associated with early gene therapy approaches.

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