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Johns Hopkins scientists crack genetic code for form of pancreatic cancer
Date:1/21/2011

are individual chemicals called nucleotides, which pair together in a pre-programmed fashion to build DNA and, in turn, a genome. Combinations of these nucleotide letters form genes, which provide instructions that guide cell activity. Changes in the nucleotide pairs, called mutations, can create coding errors that transform a normal cell into a cancerous one.

In the first set of experiments, the Johns Hopkins scientists sequenced nearly all protein-encoding genes in 10 of the 68 samples of pancreatic neuroendocrine tumors and compared these sequences with normal DNA from each patient to identify tumor-specific changes or mutations.

In another set of experiments, the investigators searched through the remaining 58 pancreatic neuroendocrine tumors to determine how often these mutated genes appeared.

The most prevalent mutation, in the MEN-1 gene, occurred in more than 44 percent of all 68 tumors. MEN-1, which has been previously linked to many cancers, creates proteins that regulate how long strands of DNA are twisted and shaped into dense packets that open and close depending on when genes need to be activated. Such a process is regulated by proteins and chemicals that operate outside of genes, termed "epigenetic" by scientists.

Two other commonly mutated genes, DAXX and ATRX, which had not previously been linked to cancer, also have epigenetic effects on how DNA is read. Of the samples studied, mutations in DAXX and ATRX were found in 25 percent and 17.6 percent, respectively. The proteins made by these two genes interact with specific portions of DNA to alter how its chemical letters are read.

"To effectively detect and kill cancers, it may be important to develop new diagnostics and therapeutics that take aim at both epigenetic and genetic processes," says Kenneth Kinzler, Ph.D., professor of oncology at the Johns Hopkins Kimmel Cancer Center and co-director of the Ludwig Center at Johns Hopkins.

The Joh
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Contact: Vanessa Wasta
wasta@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
Source:Eurekalert

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