Genetic reconnaissance identifies new colon cancer genes

In a study that realizes the promise of the investment in the Human Genome Project, Howard Hughes Medical Institute researchers have combed through a catalog of all known tyrosine kinase enzymes to identify new gene mutations that occur in a significant fraction of colon cancers.

Researchers have known for years that abnormal activity of tyrosine kinases can hasten the development of certain forms of cancer. In this first-of-a-kind survey, researchers used a forward-looking approach to screen the genes that produce tyrosine kinases -- reasoning that somewhere in this genomic landscape they might encounter novel mutations that spur colon cancer and other types of cancer.

The researchers -- including Howard Hughes Medical Institute investigators Bert Vogelstein and Sanford Markowitz-- published their findings in the May 9, 2003, issue of the journal Science. Vogelstein is at the Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University, and Markowitz is at Case Western Reserve University and University Hospitals of Cleveland.

The starting point for the studies was a detailed catalog of all kinases in the cell, similar to one published in December 2002 in the journal Science by Tony Hunter and his colleagues at the Salk Institute for Biological Studies and collaborators at the biotechnology company SUGEN.

Kinases are enzymes that activate other proteins by adding a phosphate group to them. According to Vogelstein, this catalog, which its developers named the "kinome," constitutes an ideal collection of targets for cancer researchers seeking to stop the uncontrolled proliferation of cancer cells.

"The good news is that many of the genes responsible for common cancers, like colon cancer, have been identified," said Vogelstein. "The bad news is that most of these gene

Contact: Jim Keeley
Howard Hughes Medical Institute

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