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Researchers at the University of Chicago Medicine have discovered a new way to identify potentially high-risk pediatric neuroblastoma tumors, according to research published today in the American Society of Clinical Oncology's JCO Precision Oncology journal.
Neuroblastoma is one of the most common cancers in childhood, typically occurring in the abdomen or chest of patients. It accounts for 6 percent of all pediatric cancers, with about 800 new cases diagnosed each year, according to the American Cancer Society. Currently, only 50 percent of those who are diagnosed with high-risk cases will survive in the long term.
"Neuroblastoma is an especially challenging disease to develop precision treatment strategies, because unlike in cancers that commonly affect adults, neuroblastoma tumors have few DNA mutations that would help us predict who will to respond to certain therapies," said Mark Applebaum, MD, an assistant professor of pediatrics at UChicago Medicine and first author of the new study.
Tissue samples from consenting patients were used with a relatively new technology developed at the University of Chicago by chemistry professor Chuan He. Called Nano-hmC-Seal, this low-cost, genome-wide technology requires minimal amounts of tissue input to analyze the DNA profiles.
The profiles of a DNA modification called 5-hydroxymethylcytosine (5-hmC), which has the power to switch genes on and off, have been found in recent years to be strong biomarkers, or indicators, for how adult cancers will act. Researchers in the study identified 577 genes with differential 5-hmC. Using this information, they were able to identify two clusters of patients, or "favorable" and "unfavorable" clusters.
"We determined that 5-hmC profiles may be optimal DNA-based biomarkers for this disease," said Applebaum. "A deeper dive into the process of how these 5-hmC profiles reflect aggressive tumor biology can help us better understand the characteristics of our patients' tumors in order to tailor their therapy more precisely."
Applebaum said he and his team hope their research will lead to therapies that are better targeted to the different mechanisms that cause neuroblastoma tumors to become so deadly. They are also using the Nano-hmC-Seal technology in blood samples to get better at earlier identification of patients who are responding to standard therapy and those who may benefit from alternate approaches.
In addition to Mark A. Applebaum, MD, authors of the paper include: Erin K. Barr, MD; Jason Karpus, PhD; Ji Nie, PhD; Zhou Zhang, MS, PhD; Amy E. Armstrong, MD; Sakshi Uppal, PhD; Madina Sukhanova, PhD; Wei Zhang, PhD; Alexandre Chlenski, PhD; Helen R. Salwen; Emma Wilkinson; Marija Dobratic MS; Robert Grossman, PhD; Lucy A. Godley, MD, PhD; Barbara E. Stranger, PhD; Chuan He, PhD; and Susan L. Cohn, MD.
Mark Applebaum, MD, is an expert in pediatric cancers and blood diseases. He has a special interest in the treatment of neuroblastoma, sarcomas and solid tumors.Read Dr. Applebaum's physician profile