Lustgarten Foundation funded researchers discover new mutations in pancreatic cancer

"The new data adds depth to our understanding of things that go awry in critical cellular pathways as a result of mutations, sometimes promoting cancer formation, other times providing cancer cells with advantages that enable them to crowd out healthy cells," said David Tuveson, M.D., Ph.D., Director of Research for the Lustgarten Foundation and Director of Cold Spring Harbor Laboratory Cancer Center. 

The researchers looked for mutations only in small segments of DNA called promoters, in samples of tumors taken from 308 pancreatic cancer patients. Promoters usually lie adjacent to genes whose activity they help regulate.  An activated promoter can switch "on" the gene it sits next to.  One of many causes of cancer are genes that stay "on" for too long, bypassing natural signals to shut down.  This is one way cancers grow out of control.    

Using a newly developed algorithm, the team discovered that while the promoter mutations they discovered were not near known pancreatic cancer genes, they affected some of the same biological pathways inside cancer cells.  Prominent among these were promoters affecting pathways that control cell adhesion and axon guidance.

Cell adhesion pathways help determine whether cells stick together or can fly free of the tissue in which they live.  Cancerous cells that do not adhere to moorings in tissue can become the seeds of metastasis – the often deadly situation in which loose cancer cells colonize other parts of the body. 

The axon guidance pathway associated with promoter mutations has a less obvious but no less important role in pancreatic cancer.  "In pancreas cancer, nerves are often attracted to or get attracted to the tumor," explains Michael Feigin, Ph.D., a postdoctoral researcher who led the experiments in the Tuveson lab, "and sometimes they grow right through the tumor.  This is one of the reasons pancreas cancer is so painful." Tumors, he also notes, can actually spread via nerves; this is called peri-neural invasion.

It's possible, Feigin says, that axon guidance signals – and indeed cell adhesion signals – "are actually being used by tumor cells" to gain advantages over healthy cells. 

While further exploration is required, the importance of this new knowledge about promoter mutations is that it can help researchers find new ways to fight pancreatic cancer, one of the major cancer types that remains profoundly resistant to all existing treatments.

"Recurrent noncoding regulatory mutations in pancreatic ductal adenocarcinoma" appears May 8^th in Nature Genetics. The authors are: Michael E. Feigin, Tyler Garvin, Peter Bailey, Nicola Waddell, David K. Chang, David R. Kelley, Shimin Shuai, Steven Gallinger, John D. McPherson, Sean M. Grimmond, Ekta Khurana, Lincoln D. Stein, Andrew V. Biankin, Michael C. Schatz, and David A. Tuveson.  The paper can be accessed at: http://www.nature.com/ng/index.html   

About the Lustgarten Foundation

The Lustgarten Foundation is America's largest private foundation dedicated to funding pancreatic cancer research. Based in Bethpage, N.Y., the Foundation supports research to find a cure for pancreatic cancer, facilitates dialogue within the medical and scientific community, and educates the public about the disease through awareness campaigns and fundraising events. Since its inception, the Lustgarten Foundation has directed $132 million to research and assembled the best scientific minds with the hope that one day, a cure can be found. Thanks to private funding, 100 percent of every dollar donated to the Foundation goes directly to pancreatic cancer research. For more information, please visit www.lustgarten.org.

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. Home to eight Nobel Prize winners, the private, not-for-profit Laboratory employs 1,100 people including 600 scientists, students and technicians. The Meetings & Courses Program hosts more than 12,000 scientists from around the world each year on its campuses in Long Island and in Suzhou, China. The Laboratory's education arm also includes an academic publishing house, a graduate school and programs for middle and high school students and teachers. For more information, visit www.cshl.edu

SOURCE The Lustgarten Foundation for Pancreatic Cancer Research

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