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Revising the timeline for deadly pancreatic cancer
Date:10/27/2010

, the majority of these mutations 64 percent on average were also present in the primary tumor. The researchers then worked with Martin Nowak, an evolutionary biologist at Harvard, to estimate how long it took these mutations to accumulate. Using a "molecular clock" technique commonly used in evolutionary biology, it is possible to generate a hypothesis about when a mutation occurred. By comparing the genomes of, say, monkeys and man, evolutionary biologists can estimate how long ago the two species diverged.

Similarly, each genetic mutation seen in a cancer cell represents a tick of the molecular clock. Because such mutations accumulate at a steady rate as observed in cancer cells growing in petri dishes - Vogelstein and his colleagues could estimate how long it took for all of the mutations seen in each metastatic lesion to appear.

The technique showed that it took a surprisingly long time 11.7 years on average for a mature pancreatic tumor to form after the appearance of the first cancer-related mutation in a pancreatic cell. Another 6.8 years passed, on average, before the primary tumor sent out a metastatic lesion to another organ. From that point, another 2.7 years went by, on average, before the patient died. In total, more than 20 years elapsed between the appearance of the first mutated pancreatic cell and death.

"This time scale is similar to what we've previously seen in colorectal cancers," says Vogelstein. "These tumors evolve over long periods --decades."

Unlike other cancers, though, pancreatic tumors usually produce no symptoms until they've spread. Jaundice is often the first symptom, but that arrives only after a pancreatic tumor has metastasized to the liver. But Vogelstein says the new data suggest that a blood or stool test might be able to pick up early cancer-causing mutations. His team is already examining the efficacy of such tests for detecting early signs of colorectal cancer.

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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
Source:Eurekalert

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