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!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy