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Activating SRC mutation in a subset of advanced human colon cancers

R B Irby1, W Mao, D Coppola

  • 1Department of Surgery, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida College of Medicine, Tampa 33612, USA.

Nature Genetics
|February 13, 1999
PubMed

Insights

Activating mutations in the SRC gene are found in advanced colon cancer, promoting tumor growth and metastasis. This discovery provides genetic evidence for SRC

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Rous sarcoma virus (RSV) discovery led to cellular Src (c-Src), a non-receptor tyrosine kinase implicated in human cancers.
  • c-Src is highly activated in colon cancers, especially those with liver metastasis.
  • c-Src regulation involves carboxy-terminal tyrosine phosphorylation (Tyr 530), with implications for activating mutations.

Purpose of the Study:

  • To identify and characterize activating mutations in the SRC gene in advanced human colon cancer.
  • To investigate the role of these mutations in tumor progression, metastasis, and transformation.

Main Methods:

  • Genetic analysis to identify mutations in the SRC gene in colon cancer patients.
  • Functional assays to assess the kinase activity, transforming potential, tumorigenicity, and metastatic ability of the identified SRC mutation.

Main Results:

  • A truncating mutation in SRC at codon 531 was identified in 12% of advanced colon cancer cases.
  • This SRC mutation was demonstrated to be activating, transforming, tumorigenic, and to promote metastasis.

Conclusions:

  • Activating SRC mutations, specifically the codon 531 truncation, play a role in the malignant progression of human colon cancer.
  • This provides the first genetic evidence linking activating SRC mutations to colon cancer metastasis.

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