Hopkins team identifies genetic code for rare pancreatic cancer
Researchers at Johns Hopkins have found the genetic code for a type of pancreatic cancer that can help predict the disease.
Understanding which genes misbehave and lead to cancer means better treatment options and understanding of how cancer will behave. The scientists were able to "map" the genetic code for a rare type of pancreatic cancer, called neuroendocrine or islet cell tumors, that can help predict how aggressive the cancer is, what treatments are likely to work, and survival rates.
Nickolas Papadopoulos, Ph.D., associate professor at the Johns Hopkins Kimmel Cancer Center and director of translational genetics at Hopkins’ Ludwig Center says, “One of the most significant things we learned is that each patient with this kind of rare cancer has a unique genetic code that predicts how aggressive the disease is and how sensitive it is to specific treatments.”
Approaching cancer treatment based on genetic differences in tumors types can lead to more personalized care. Neuroendocrine pancreatic cancer accounts for 5 percent of all cases, and some produce different symptoms. Others have no “hormone signal” and grow silently, according to Ralph Hruban, M.D., professor of pathology and oncology, and director of the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins.
“This is a great example of the potential for personalized cancer therapy,” says Hruban. “Patients who are most likely to benefit from a drug can be identified and treated, while patients whose tumors lack changes in the mTOR pathway could be spared the side effects of drugs that may not be effective in their tumors.”
In the study, 68 men and women were investigated who had non-hormonal pancreatic neuroendocrine tumors. Those who had MEN-1, DAXX and ATRX gene mutations lived at least 10 years after being diagnosed. Patients who did not have the genetic mutation died within 5 years.
The researchers conducted two sets of experiments to find the genetic code in neuroendocrine pancreatic cancers. In the first study, they compared normal DNA to 10 of the 68 pancreatic neuroendocrine tumors to find mutations specific to each. In the second set of experiments, they looked at how often the gene mutations appeared.
In 68 of the tumors, the MEN-1 gene, occurred more than 44 percent of the time, making it the most prevalent. The MEN-1 gene is linked to other types of cancer, and creates proteins that regulate the shape of DNA. The process occurs outside of genes through epigenetics.
Kenneth Kinzler, Ph.D., professor of oncology at the Johns Hopkins Kimmel Cancer Center and co-director of the Ludwig Center at Johns Hopkins, explains, “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.”
The researchers previously identified the genomes of 6 other types of cancer by identifying individual chemicals called nucleotides that pair up in a pre-programmed fashion to build DNA and, in turn, genomes. Changes in the way nucleotides team up can lead to mutations that cause cancer.
The researchers use an automated mapping tool to find the genetic code within cancer cells. In the study, they also found a 25 percent mutation in DAXX and 17.6% percent ATRX genes. They explain, “The proteins made by these two genes interact with specific portions of DNA to alter how its chemical letters are read.”
Finding genetic coding “mistakes” that make up individual types of cancer can predict outcomes and lead to improved cancer treatment. Understanding the genetic code for the rare type of pancreatic cancer opens the door for new therapies.
By cracking the genetic code of neuroendocrine pancreatic cancer, scientists learned patients with certain coding mistakes live twice as long as patients without the gene type. The findings are due for publication today in the journal Science.