In a genome sequencing study of 74 neuroblastoma tumors in children, scientists at the Johns Hopkins Kimmel Cancer Center and the Children's Hospital of Philadelphia (CHOP) found that patients with changes in two genes, ARID1A and ARID1B, survive only a quarter as long as patients without the changes. The discovery could eventually lead to early identification of patients with aggressive neuroblastomas who may need additional treatments.
Neuroblastomas affect nerve tissue throughout the body and are the most common, non-blood cancer in children. "These cancers have a wide spectrum of clinical outcomes, with some that are highly curable and others very lethal," says Victor Velculescu, M.D., Ph.D., professor of oncology and co-director of the Cancer Biology Program at Johns Hopkins. "Part of the reason for this variety in prognosis may be due to changes in the ARID1A and ARID1B genes."
Velculescu said these powerful "bully" genes were not identified in other gene sequencing studies of neuroblastoma, most likely because the Johns Hopkins-CHOP researchers used sequencing and analytical methods that looked for larger, structural rearrangements of DNA in addition to changes in the sequence of individual chemical base-pairs that form DNA. A report of their work appears in the Dec. 2 issue of Nature Genetics.
Of the 74 tumors in the study, 71 were analyzed for both rearrangements and base-pair changes. Cancer-specific mutations were found in a variety of genes previously linked to neuroblastoma, including the ALK and MYCN genes. In eight of the 71 patients, the investigators found alterations in the ARID1A and ARID1B genes, which normally control the way DNA folds to allow or block protein production.
The children with ARID1A or ARID1B gene changes had far worse survival, on average, than those without the genetic alterations — 386 days compared with 1,689 days. All but one of these patients died of progressive disease, including one child whose neuroblastoma was thought to be highly curable.
The scientists were also able to detect and monitor neuroblastoma-specific genetic changes in the blood of four patients included in the study, and correlated these findings to disease progression.
"Finding cancer-specific alterations in the blood could help clinicians monitor patients for relapse and determine whether residual cancer cells remain in the body after surgery," says Mark Sausen, a Johns Hopkins graduate student and one of the lead scientists involved in the research.
The Johns Hopkins-CHOP team plans to conduct further studies in larger groups of patients to confirm the ARID1A-ARID1B correlation to prognosis.
Funding for the study was provided by the St. Baldrick's Foundation, the Virginia and D.K. Ludwig Fund for Cancer Research, Swim Across America, the American Association for Cancer Research – Stand Up To Cancer's Dream Team Translational Cancer Research Grant, and the National Institutes of Health's National Cancer Institute (CA121113).
In addition to Velculescu and Sausen, scientists involved in the research include Rebecca Leary, Sian Jones, Jian Wu, Amanda Blackford, Luis Diaz, Nickolas Papadopoulos, Bert Vogelstein, and Kenneth Kinzler from Johns Hopkins; C. Patrick Reynolds from Texas Tech University Health Sciences Center; Giovanni Parmigiani from the Dana-Farber Cancer Institute; and Michael Hogarty and Xueyuan Liu from the Childrens Hospital of Philadelphia.Papadopoulos, Kinzler, Vogelstein, Diaz and Velculescu are co-founders of Inostics and Personal Genome Diagnostics and are members of the companies' Scientific Advisory Boards. They own Inostics and Personal Genome Diagnostics stock, which is subject to certain restrictions under Johns Hopkins University policy. The terms of these arrangements are managed by The Johns Hopkins University in accordance with its conflict-of-interest policies.
Vanessa Wasta | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences