Genetic Blueprint for Pancreatic Cancer

In an exciting advance, the complete genetic blueprint for pancreatic cancer, one of the most lethal of all of the cancers, was decoded by a team at the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins. The study, led by Drs. Vogelstein, Kinzler and Velculescu, is reported in the Sept. 5, 2008, issue of Science Express.

The team sequenced more than 20,000 genes in a series of 24 well-characterized pancreatic cancers and discovered over 1,500 DNA mutations in these cancers. An average of 63 mutations was found in each cancer, supporting the growing body of evidence that cancer is fundamentally a disease caused by alterations in the DNA. The complex picture presented by these mutations was simplified by the finding that many of them acted in concert through a set of well-defined signaling pathways and processes. The scientists identified 12 core signaling pathways and processes that were each altered in more than two-thirds of the cancers. These 12 core pathways provide the basis for novel diagnostic and therapeutic approaches in pancreatic cancer.

As a part of the study the team also discovered over 500 genes that were made at abnormally high levels in the 24 cancers. Fifty-four of these over expressed genes were predicted to be secreted or made on the surface of the cancer cells, suggesting that these genes may be useful therapeutic targets or may form the basis for new tests for the early detection of pancreatic cancer.

The landmark study characterizes the fundamental genetic components of pancreatic cancer and will guide research on this disease for the next decade. The improved understanding realized from these studies, and their follow-up work will hopefully lead to dramatic improvements in the prevention, detection, or treatment of pancreatic cancer.

The project is also a great example of the power of private giving. The major funding The Pancreatic Cancer Genome Project came from the Sol and Lillian Goldman Charitable Trusts. Significant funding also came from The Lustgarten Foundation for Pancreatic Cancer Research. Additional funding came from the Virginia and D. K. Ludwig Fund, Susan G. Komen Foundation, Michael Rolfe Pancreatic Cancer Foundation, Joseph C. Monastra Foundation, the family and friends of George Rubis, Viragh Family Foundation, Broad Foundation, Emerald Foundation, and National Institutes of Health.

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