Distinctive genetic program guides breast cancer's deadly spread

Researchers have peered inside breast cancer's toolbox and identified a set of rogue genes that accelerates the spread of cancer from its primary site in the breast to a secondary location in bone marrow. The genes identified by the scientists are distinct from those that spawn the initial tumor, which invites speculation about whether different cancers bear unique "gene expression signatures" that increase the probability that a cancer will spread in a process called metastasis.

Metastasis occurs when cells from a primary tumor break off and invade another organ. It is the deadliest transformation that a cancer can undergo, and therefore researchers have been looking for specific genes that propel metastasis. If they can identify distinctive metastatic gene programs for different cancers, it may be possible to slow or halt metastases by targeting the proteins produced by those genes.

In the June 2003 issue of the journal Cancer Cell, researchers led by Howard Hughes Medical Institute investigator Joan Massagu at Memorial Sloan-Kettering Cancer Center, published a report showing that breast cancer metastasis to bone is mediated by a specific set of genes. Massagu collaborated on the studies with colleagues from the University of Texas Health Science Center.

"There has been a raging controversy in the cancer research field between two hypotheses," said Massagu. "One is the classical view that says that only a few cells in a tumor acquire alterations that render them increasingly metastatic. And of the millions of tumor cells that enter the circulation, the patient only gets a handful of metastases from these cells.

"By contrast, there has been recent evidence that primary tumors that go on to develop metastases already possess a 'poor prognosis signature' involving a group of genes whose high level of activity is indicative of the potential for metastasis," he said.

To attempt to distinguish between these two models, Massagu an

Contact: Jim Keeley
Howard Hughes Medical Institute

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