Contact Information:
Carrie Strehlau
carrie.strehau@stjude.org
901-595-2295
St. Jude Children's Research Hospital



Kredyty mieszkaniowe Kredyty mieszkaniowe

Sprawdź aktualny ranking najlepszych kredytów mieszkaniowych w Polsce - atrakcyjne kredytowanie nieruchomości.
PRESS-NEWS.org - Press Release Distribution
FREE PRESS RELEASES DISTRIBUTION
RSS - Press News Release
Add Press Release

Gene sequencing project discovers mutations tied to deadly brain tumors in young children

St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project offers new leads to improved outcomes for children with high-grade glioma brain tumors; particularly youngest patients


2014-04-07
(Press-News.org) (MEMPHIS, TENN. - April 6, 2014) The St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project has identified new mutations in pediatric brain tumors known as high-grade gliomas (HGGs), which most often occur in the youngest patients. The research appears today as an advance online publication in the scientific journal Nature Genetics.

The discoveries stem from the most comprehensive effort yet to identify the genetic missteps driving these deadly tumors. The results provide desperately needed drug development leads, particularly for agents that target the underlying mutations. This and other studies show these mutations often differ based on patient age. HGGs represent 15 to 20 percent of brain and spinal tumors in children. Despite aggressive therapy with surgery, radiation and chemotherapy, long-term survival for HGG patients remains less than 20 percent.

The study is one of four being published simultaneously in the same issue of Nature Genetics that link recurring mutations in ACVR1 to cancer for the first time. Pediatric Cancer Genome Project researchers found that ACVR1 was mutated in 32 percent of 57 patients diagnosed with a subtype of HGG called diffuse intrinsic pontine glioma (DIPG). While DIPGs are usually found in children ages 5 to 10, ACVR1 mutations occurred most frequently in younger-than-average patients. DIPG occurs in the brainstem, which controls vital functions and cannot be surgically removed.

The investigators also identified alteration in NTRK genes that drove tumor development in young HGG patients whose tumors developed outside the brainstem. This study included 10 patients who were age 3 or younger when they were diagnosed with such non-brainstem HGGs. Of those, 40 percent had tumors with alterations in one of three NTRK genes and few other changes. The alterations occurred when a segment of the NTRK genes involved in regulating cell division fused with part of another gene.

"These results indicate the NTRK fusion genes might be very potent drivers of cancer development that have the ability to generate tumors with few other mutations," said co-corresponding author Suzanne Baker, Ph.D., a member of the St. Jude Department of Developmental Neurobiology. The other corresponding author is Jinghui Zhang, Ph.D., a member of the St. Jude Department of Computational Biology. "We want to see if these tumors might be selectively sensitive to therapies that target the pathways that are disrupted as a result of these fusion genes," Baker said.

Added co-author Richard K. Wilson, Ph.D., director of The Genome Institute at Washington University School of Medicine in St. Louis: "We've made some very exciting discoveries that likely will result in more effective diagnosis and treatment of these particularly nasty tumors."

In this study, researchers analyzed 127 HGGs from 118 pediatric patients, including whole genome sequencing of the complete tumor and normal DNA from 42 patients. More targeted sequencing of additional tumors was conducted to track how instructions encoded in DNA were translated into the proteins that do the work of cells.

The recurring presence of ACVR1 mutations in a subset of DIPG patients was one of the biggest surprises, Baker said. ACVR1 carries instructions for making a protein receptor on the cell membrane. The receptor functions as an on-off switch for a biochemical pathway named bone morphogenetic protein, or BMP. The pathway helps regulate growth and development of bone and other tissue. Working in zebra fish and mouse brain cells, researchers found evidence that ACVR1 mutations from DIPG resulted in the BMP pathway being inappropriately and permanently switched on.

In individuals with an inherited disorder called fibrodysplasia ossificans progressiva (FOP), the same ACVR1 mutations lead not to cancer, but to a different mechanism resulting in abnormal growth of bone in other tissues. Patients with FOP carry the ACVR1 mutation in every cell, while the gene is mutated only in the tumor cells of DIPG patients. "The same mutations are doing something very different in these two terrible and rare diseases. We are working to understand not only how the mutations contribute to cancer, but also whether blocking the BMP pathway offers a new way to treat the tumor," Baker said.

The ACVR1 mutations often occurred with mutations in a gene that carries instructions for making the histone H3.1 protein. That protein influences gene activity through its role in packaging DNA in the nucleus. Mutations in the histone H3 family of proteins were first reported in an earlier Pediatric Cancer Genome Project study. Baker said the new findings suggest the two mutations work together to give tumor cells a selective advantage in the developing brainstem.

While the ACVR1 mutations occurred only in tumors in the brainstem, the NTRK fusion genes were found in HGGs that developed throughout the brain. By combining pieces of different genes, fusion genes can lead to production of abnormal proteins that disrupt cell function. Fusion genes were identified in almost half of all pediatric HGGs in this study, but the NTRK fusions were the most common. The NTRK fusions involved a gene segment encoding a tyrosine kinase domain. This domain functions as an on-off switch for several important regulatory mechanisms in cells that often malfunction in cancer cells.

NTRK fusion genes have been identified in other pediatric and adult brain tumors. This study marks the first report of the genes in pediatric HGGs. The NTRK fusion genes were identified in part through targeted sequencing of RNA. RNA molecules help translate the instructions carried in DNA into the proteins that do the work of cells. This study was the first to include RNA sequencing in an analysis of HGGs.

The study was part of the Pediatric Cancer Genome Project, which has sequenced the complete normal and tumor genomes of 700 young cancer patients. The project was launched in 2010 to harness advances in genome sequencing technology to improve understanding and treatment of some of the most aggressive and least understood childhood cancers.

INFORMATION: The study's first authors are Gang Wu and Alexander Diaz, both of St. Jude. The other authors are Barbara Paugh, Sherri Rankin, Bensheng Ju, Yongjin Li, Xiaoyan Zhu, Chunxu Qu, Xiang Chen, Junyuan Zhang, John Easton, Michael Edmonson, Xiaotu Ma, Panduka Nagahawatte, Erin Hedlund, Michael Rusch, Stanley Pounds, Tong Lin, Arzu Onar-Thomas, Robert Huether, Richard Kriwacki, Matthew Parker, Pankaj Gupta, Jared Becksfort, Heather Mulder, Kristy Boggs, Bhavin Vadodaria, Donald Yergeau, Frederick Boop, Alberto Broniscer, Cynthia Wetmore, Amar Gajjar, Michael Taylor, James Downing and David Ellison, all of St. Jude; Jake Russell, formerly of St. Jude; Charles Lu, Kerri Ochoa, Robert Fulton, Lucinda Fulton, Li Ding and Elaine Mardis, all of Washington University; Lei Wei of Roswell Park Cancer Institute, Buffalo, N.Y.; and Chris Jones of the Institute for Cancer Research, London.

The study was funded in part by the Pediatric Cancer Genome Project, including Kay Jewelers, a lead sponsor; grants (CA096832, CA135554) from the National Institutes of Health, The Cure Starts Now Foundation, Smile for Sophie Forever Foundation, Tyler's Treehouse, Musicians Against Childhood Cancer and ALSAC.

St. Jude Media Relations Contacts

Carrie Strehlau
(desk) (901) 595-2295
(cell) (901) 297-9875
carrie.strehlau@stjude.org Summer Freeman
(desk) (901) 595-3061
(cell) (901) 297-9861
summer.freeman@stjude.org

Washington University Media Relations Contact Caroline Arbanas
(cell) 314-445-4172
(desk) 314-286-0109
arbanasc@wustl.edu

ELSE PRESS RELEASES FROM THIS DATE:

Renewable energy market share climbs despite 2013 dip in investments

Renewable energy market share climbs despite 2013 dip in investments
2014-04-07
Frankfurt / New York, 7 April 2014 – Renewable energy's share of world electricity generation continued its steady climb last year despite a 14 per cent drop in investments to US$214.4 billion, according to a new report released today. According to Global Trends in Renewable Energy Investment 2014 – produced by the Frankfurt School-UNEP Collaborating Centre for Climate & Sustainable Energy Finance, the United Nations Environment Programme (UNEP) and Bloomberg New Energy Finance — the investment drop of $US35.1 billion was partly down to the falling cost of solar photovoltaic ...

US schoolchildren exposed to arsenic in well water have lower IQ scores

2014-04-07
NEW YORK (April 7, 2014)—A study by researchers at Columbia University reports that schoolchildren from three school districts in Maine exposed to arsenic in drinking water experienced declines in child intelligence. While earlier studies conducted by the researchers in South Asia, and Bangladesh in particular, showed that exposure to arsenic in drinking water is negatively associated with child intelligence, this is the first study to examine intelligence against individual water arsenic exposures in the U.S. Findings are reported online in the journal, Environmental ...

Twitter use linked to infidelity and divorce, MU study finds

2014-04-07
COLUMBIA, Mo. – Twitter and other social networking services have revolutionized the way people create and maintain relationships. However, new research shows that Twitter use could actually be damaging to users' romantic relationships. Russell Clayton, a doctoral student in the University of Missouri School of Journalism, found that active Twitter users are far more likely to experience Twitter–related conflict with their romantic partners. Clayton's results showed that Twitter-related conflict then leads to negative relationship outcomes, including emotional and physical ...

No evidence of AD-associated changes in adolescents carrying genetic risk factors

2014-04-07
Amsterdam, NL, April 7, 2014 – Two studies published in the Journal of Alzheimer's Disease indicate that some of the pathologic changes associated with Alzheimer's disease in older individuals are not apparent in young people who carry the apolipoprotein (APOE) genetic risk factor for developing the disease. In the first study, no differences were found in hippocampal volume or asymmetry between cognitively normal adolescent carriers and non-carriers of the ApoE ɛ4 or ɛ2 allelles. The second study reports no differences in plasma concentrations of amyloid-β ...

Parental obesity and autism risk in the child

2014-04-07
Several studies have looked at possible links between maternal obesity during pregnancy and the risk of developmental disorders in the child. However, paternal obesity could be a greater risk factor than maternal obesity, according to a new study from the Norwegian Institute of Public Health. As the first researcher to study the role of paternal obesity in autism, Dr. Pål Surén emphasises that this is still a theory and requires much more research before scientists can discuss possible causal relationships. "We have a long way to go. We must study genetic factors ...

Fatty acid composition in blood reflects the quality of dietary carbohydrates in children

2014-04-07
Recently published research in the University of Eastern Finland found that fatty acid composition in blood is not only a biomarker for the quality of dietary fat but also reflects the quality of dietary carbohydrates. For example the proportion of oleic acid was higher among children who consumed a lot of candy and little high-fibre grain products. Earlier studies on the topic have mainly concentrated on the association of the quality of dietary fat with fatty acid composition in blood. In the present study, the association of the quality of dietary carbohydrates with ...

Why do we get allergies? The science of springtime sniffling and sneezing (video)

Why do we get allergies? The science of springtime sniffling and sneezing (video)
2014-04-07
WASHINGTON, April 7, 2014 — Spring has sprung, and with it comes blooming flowers, shorts and t-shirts and, for the millions who suffer from allergies, a runny nose, puffy eyes and general misery. In the American Chemical Society's (ACS') latest Reactions video, we explain the science behind the allergies that spoil spring for so many people. The video is available at http://youtu.be/vFZlxQU0Pyk. INFORMATION: Subscribe to the series at Reactions YouTube, and follow us on Twitter @ACSreactions to be the first to see our latest videos. The American Chemical Society ...

Health benefits of 'green exercise' for kids shown in new study

2014-04-07
Children who are exposed to scenes of nature while exercising are more likely to experience health-enhancing effects after activity, according to a Coventry University study published this week in the International Journal of Environmental Research and Public Health. Sports science academics in the University's Department of Applied Sciences and Health asked kids aged 9-10 years to complete a series of 15 minute moderate intensity cycling activities – one whilst viewing a video of a forest track synced to the exercise bike and another with no visual stimulus. The researchers ...

Energizing sick mitochondria with vitamin B3

2014-04-07
Vitamins B have recently been turned out to be potent modifiers of energy metabolism, especially the function of mitochondria. Vitamin B3, (niacin) has been found to delay the signs of aging in animal models. An international collaboration between the University of Helsinki and École Polytechnique Fédérale de Lausanne reported today in the high-profile journal, Embo Molecular Medicine, that vitamin B3 form, nicotinamide riboside, can slow down the progression of mitochondrial disease, suggesting its potential as a novel therapy approach to adult-onset mitochondrial ...

Organic solar cells more efficient with molecules face-to-face

Organic solar cells more efficient with molecules face-to-face
2014-04-07
New research from North Carolina State University and UNC-Chapel Hill reveals that energy is transferred more efficiently inside of complex, three-dimensional organic solar cells when the donor molecules align face-on, rather than edge-on, relative to the acceptor. This finding may aid in the design and manufacture of more efficient and economically viable organic solar cell technology. Organic solar cell efficiency depends upon the ease with which an exciton – the energy particle created when light is absorbed by the material – can find the interface between the donor ...

LAST 30 PRESS RELEASES:

How your brain decides blame and punishment -- and how it can be changed

Uniquely human brain region enables punishment decisions

Pinpointing punishment

Chapman University publishes research on attractiveness and mating

E-cigarettes: Special issue from Nicotine & Tobacco Research

Placental problems in early pregnancy associated with 5-fold increased risk of OB & fetal disorders

UT study: Invasive brood parasites a threat to native bird species

Criminals acquire guns through social connections

Restoring ocean health

Report: Cancer remains leading cause of death in US Hispanics

Twin study suggests genetic factors contribute to insomnia in adults

To be fragrant or not: Why do some male hairstreak butterflies lack scent organs?

International team discovers natural defense against HIV

Bolivian biodiversity observatory takes its first steps

Choice of college major influences lifetime earnings more than simply getting a degree

Dominant strain of drug-resistant MRSA decreases in hospitals, but persists in community

Synthetic biology needs robust safety mechanisms before real world application

US defense agencies increase investment in federal synthetic biology research

Robots help to map England's only deep-water Marine Conservation Zone

Mayo researchers identify protein -- may predict who will respond to PD-1 immunotherapy for melanoma

How much water do US fracking operations really use?

New approach to mammograms could improve reliability

The influence of citizen science grows despite some resistance

Unlocking secrets of how fossils form

What happens on the molecular level when smog gets into the lungs?

Using ultrasound to clean medical instruments

Platinum and iron oxide working together get the job done

Tiny silica particles could be used to repair damaged teeth, research shows

A quantum lab for everyone

No way? Charity's logo may influence perception of food in package

[Press-News.org] Gene sequencing project discovers mutations tied to deadly brain tumors in young children
St. Jude Children's Research Hospital-Washington University Pediatric Cancer Genome Project offers new leads to improved outcomes for children with high-grade glioma brain tumors; particularly youngest patients
Press-News.org is a service of DragonFly Company. All Rights Reserved.
Issuers of news releases are solely responsible for the accuracy of their content.