Scientists develop method to determine order of mutations that lead to cancer

June 30, 2011

Zeroing in on the early cell mutations that enable a cancer to grow is one of the best ways to find a personalized therapy to stop it. Scientists were able to use a statistical approach for the first time to map out the order in which these abnormalities form to analyze the pattern of DNA changes in advanced skin and ovarian tumors.

The study's findings, which are published in the July edition of Discovery, are the result of a collaboration of scientists at the Oregon Health & Science University Knight Cancer Institute; the Lawrence Berkeley National Laboratory, the University of California, San Francisco; and the Samsung Advanced Institute of Technology.

The researchers focused on assessing mutations involving TP53, a gene that normally prevents cells from becoming cancerous. By examining how additional copies of the mutant gene accumulated, they found that changes in TP53 occurred earlier in the disease's progression than previously believed.

Cancers are the result of multiple mutations, but the ones that happen first set the stage for additional abnormalities.

"We anticipate that this information will enhance our ability to detect cancer early when it is more likely to respond well to treatment," said Joe Gray, Ph.D., associate director for translational research for the OHSU Knight Cancer Institute.

Early mutations are also important because they are found in every cell of the cancer. "By understanding what happens early in a tumor's growth, you can develop therapies that will target all cancer cells," said Paul Spellman, Ph.D., of the Lawrence Berkeley National Laboratory and one of the lead scientists on the study. Spellman will join the OHSU Knight Cancer Institute in July.

Getting information about the order in which aberrations occur previously was difficult because it required the ability to analyze tumors as they developed. But, many cancers aren't detected until they've progressed beyond the initial growth phase. The researchers got around this problem by developing a novel statistical strategy. They integrated measurements of mutations with measurements of structural variations in a genome, which result in the cell having abnormal numbers of copies of one or more sections of DNA. "Now we have an ordering tool that should be broadly useful," Gray said.

So far, the researchers have investigated only a few types of cancer. Going forward, the analysis could be applied to all cancers. One near-term goal, Gray said, is to identify early for which there are therapies already available.

Explore further: New class of cancer drugs could work in colon cancers with genetic mutation, study finds

Related Stories

Kidney cancer discovery could expand treatment options

June 1, 2011

Oregon Health & Science University Knight Cancer Institute researchers uncovered a gene that may be the key to helping kidney cancer patients who don't respond to current therapies. This discovery could also provide a toolkit ...

A four-dimensional view of breast cancer treatment

June 8, 2011

Dr. Joe Gray, director of the Oregon Health & Science University Center for Spatial Systems Biomedicine, addressed a capacity crowd at the Environmental Molecular Sciences Laboratory Auditorium at Pacific Northwest National ...

Team decodes evolution of skin and ovarian cancer cells

June 29, 2011

A team of researchers led by scientists at the University of California, San Francisco has developed a way to uncover the evolution of human cancer cells, determining the order in which mutations emerge in them as they wend ...

Recommended for you

Researchers thwart cancer cells by triggering 'virus alert'

August 27, 2015

Working with human cancer cell lines and mice, researchers at the Johns Hopkins Kimmel Cancer Center and elsewhere have found a way to trigger a type of immune system "virus alert" that may one day boost cancer patients' ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.