October 12, 2001 -- Researchers have discovered a gene that appears to allow colon tumors to spread to other parts of the body, a process called metastasis. The gene codes for an enzyme that may be central to the metastatic process, suggesting the possibility that the enzyme could targeted by drugs to block the spread of colon cancers. Metastasis is the primary cause of death from colon cancer.

In an article published online in the October 12, 2001, edition of Science, Howard Hughes Medical Institute investigator Bert Vogelstein and colleagues at the Johns Hopkins University Oncology Center reported identifying the gene, called PRL-3.

The researchers identified PRL-3 after developing a profile of gene expression in cells they microdissected from cancers that had metastasized to the liver. The genetic profile was developed using SAGE (serial analysis of gene expression), a technique invented by the researchers to determine the level of expression of genes. In SAGE, the enzyme, reverse transcriptase, is used to produce complementary DNA from the messenger RNA (mRNA) derived from cells under study. The DNA is then snipped at a defined position, creating a unique identifier "tag" that corresponds to a single gene. The researchers can then analyze the number of unique tags present in their sample and deduce how much mRNA exists for each gene -- a measure of gene activity.

Vogelstein said that the group's initial analyses of gene expression in the metastatic tissue yielded confusing results. "When we initially took metastatic lesions from patients, purified the RNA, and then looked at their gene expression profiles, we found many of the [gene] transcripts were clearly derived from non-neoplastic cells," he said. "The problem is that tumors are composed of multiple cell types; not just the neoplastic cells. Liver metastases from colon cance
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
11-Oct-2001