Colon Cancer’s Potential for Metastasis Determined Early

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Some colon cancers are destined to spread to the liver and other parts of the body, whereas others are successfully treated by surgical removal of the tumor. Now, Howard Hughes Medical Institute investigators have found that the ability of a colon tumor to metastasize arises early in its development.

Those colon cancers that spread carry the ability to metastasize from the time they become cancerous, the researchers found. They don't need to acquire any new genetic mutations to become metastaticterm. The research also suggests that once a colon carcinomaterm develops, if it is going to spread outside the colon, it will do so in less than two years.

“Our research implies that the genetic machinery that causes metastases is hard-wired into the tumor from the beginning.”
Sanford Markowitz

“The ability to metastasize is hard-wired into this group of tumors in the colon,” said Sanford Markowitz, a Howard Hughes Medical Institute investigator at Case Western Reserve University. “It isn't something that happens after a cancer cell wanders off and leaves the colon.”

Markowitz and his colleagues published their findings in the Proceedings of the National Academy of Sciences on March 3, 2008.

Colon cancer is the second leading cause of cancer mortality in the United States, causing about 60,000 deaths annually. But there are many more cases of colon cancer that are cured by surgical removal of the tumor. Markowitz and his team wanted to understand the genetic differences between the two types.

“It's clear that colon cancer comes in two very different varieties,” said Markowitz, who led the study. “With one variety, the surgeon cuts it out and the individual is cured. With the other variety, the surgeon cuts it out but the disease still spreads, and despite our best efforts the individual succumbs to the disease. So you have two hugely different biological behaviors that are literally the difference between life and death. And we wanted to know if we could find a genetic basis for that difference.”

To do so, the team compared the DNA of primary colon tumors to the DNA of tumors in the liver that had spread from the colon - the metastases. Markowitz said he was shocked to discover that, in 7 of 10 patients, there were no new mutations in the liver tumors. That means the ability of those tumors to spread from the colon was hard-wired from their inception.

In the tumors from the other three patients, a few new genetic mutations appeared in the liver metastases. But none of the mutations appeared in more than one patient. “My guess is that these mutations are noise, that they aren't responsible for the metastases,” said Markowitz.

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