Featured Research

from universities, journals, and other organizations

Groundbreaking discovery in deadly childhood cancer

Date:
December 11, 2013
Source:
McGill University Health Centre
Summary:
A new study by Canadian researchers may pave the way for more effective treatment of an aggressive and deadly type of brain tumor, known as ETMR/ETANTR. The tumor, which is seen only in children under four, is almost always fatal, despite aggressive treatment. The study proposes a new model for how this brain tumor develops and suggests possible targets to investigate for novel therapies.

Dr. Nada Jabado and Dr. Jacek Majewski, two co-principal investigators of the study at the laboratories of the Génome Québec Innovation Centre and McGill University.
Credit: McGill University Health Centre

A new study by Canadian researchers may pave the way for more effective treatment of an aggressive and deadly type of brain tumor, known as ETMR/ETANTR. The tumor, which is seen only in children under four, is almost always fatal, despite aggressive treatment. The study proposes a new model for how this brain tumor develops and suggests possible targets to investigate for novel therapies. These findings, recently published in Nature Genetics, also shed new light on the complex process of early brain development. The study was led by the Research Institute of the McGill University Health Centre (RI-MUHC), the McGill University and Génome Québec Innovation Centre, and The Hospital for Sick Children (SickKids), and funded by the Cancer Research Society.

Related Articles


"We undertook this study because we wanted to learn what was driving the growth of these tumors and how best to treat them," says the study's co-principal investigator, Dr. Nada Jabado, hemato-oncologist at the Montreal Children's Hospital of the MUHC and an associate professor in the Department of Pediatrics at McGill University. "This is a very aggressive disease with poor outcomes for patients; we urgently need better treatments for these kids, and this study, which helps us better understand what happens in this tumor, moves us a little closer to that target."

"Our recent collaborations with Dr. Jabado's and Dr. Majewski's labs and other colleagues have provided opportunities to take our initial discovery of this entity closer to finding innovative treatments for this disease, which we believe is an important, yet under-recognized, infantile brain tumor, " says co-principal investigator Dr. Annie Huang, a brain tumor specialist at SickKids and senior scientist in Cell Biology at SickKids Research Institute and associate professor of Pediatrics at the University of Toronto. In 2009, her group had made the initial discovery that several forms of deadly brain tumors in young children were in fact this single entity (ETMR/ETANTR), characterized by a unifying genetic marker.

For the study, the research team produced "genomic" profiles of the ETMR/ETANTR tumors, and also integrated and analyzed data from five massive publicly available data sets. Their analysis suggested that, in patients with ETMR/ETANTR, a developmental pathway -- a process involved in the early formation of an organ in an embryo -- is somehow "hijacked." As a result, patients produce a specific form of an enzyme known as DNMT3B far later in development and in far greater quantities than normal.

"Genomic approaches are offering unprecedented opportunities to understand cancer," explains co-principal investigator, Dr. Jacek Majewski, associate professor in the Department of Human Genetics at McGill University and a researcher at the McGill University and Génome Québec Innovation Centre. "In the past, researchers would meticulously follow individual genes and proteins to try to piece together what goes awry in a tumor. Today, we can rapidly look at the entire genome and, using computational analysis, identify the incorrectly produced genes -- all with very little prior knowledge of the biology of the disease. In the case of the ETMR/ETANTR, within a few months we were able to go from tumor to a very promising target gene -- DNMT3B."

Abnormalities in DNMT3B have previously been linked to a range of cognitive problems. Forms of this enzyme are also seen in some leukemia and breast cancer types, and are often associated with poor outcomes. The research team found that, in patients with ETMR/ETANTR, the enzyme was present in huge quantities and at a stage of development when it should not be present at all. From a clinical point of view, the results of this study suggest DNMT3B may be a suitable target for future therapies designed to combat ETMR/ETANTR.

"We now want to see if we can control the production of the enzyme in the tumor, and if doing so enables us to stall its growth," says Dr. Jabado who is also a researcher in Medical Genetics and Genomics at the RI-MUHC.

"This is a great example of how research can produce exciting and at times groundbreaking results, and we are thrilled to have contributed to this study that will hopefully help to save children's lives, and hopefully get more studies of its kind off the ground," states Andy Chabot, President and CEO of the Cancer Research Society.

Findings from this study will be added to a global tumor registry and ETMR/ETANTR tumor bank established by Dr. Huang, which has collected nearly 100 of these rare tumors to date. Although more research is needed, the prospects for developing an effective treatment are becoming steadily brighter as scientists learn more about ETMR/ETANTR. Importantly, these findings highlight how studying rare pediatric brain tumors can provide invaluable insight into unsuspected molecular mechanisms of brain development.


Story Source:

The above story is based on materials provided by McGill University Health Centre. Note: Materials may be edited for content and length.


Journal Reference:

  1. Claudia L Kleinman, Noha Gerges, Simon Papillon-Cavanagh, Patrick Sin-Chan, Albena Pramatarova, Dong-Anh Khuong Quang, Véronique Adoue, Stephan Busche, Maxime Caron, Haig Djambazian, Amandine Bemmo, Adam M Fontebasso, Tara Spence, Jeremy Schwartzentruber, Steffen Albrecht, Peter Hauser, Miklos Garami, Almos Klekner, Laszlo Bognar, Jose-Luis Montes, Alfredo Staffa, Alexandre Montpetit, Pierre Berube, Magdalena Zakrzewska, Krzysztof Zakrzewski, Pawel P Liberski, Zhifeng Dong, Peter M Siegel, Thomas Duchaine, Christian Perotti, Adam Fleming, Damien Faury, Marc Remke, Marco Gallo, Peter Dirks, Michael D Taylor, Robert Sladek, Tomi Pastinen, Jennifer A Chan, Annie Huang, Jacek Majewski, Nada Jabado. Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR. Nature Genetics, 2013; DOI: 10.1038/ng.2849

Cite This Page:

McGill University Health Centre. "Groundbreaking discovery in deadly childhood cancer." ScienceDaily. ScienceDaily, 11 December 2013. <www.sciencedaily.com/releases/2013/12/131211131626.htm>.
McGill University Health Centre. (2013, December 11). Groundbreaking discovery in deadly childhood cancer. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2013/12/131211131626.htm
McGill University Health Centre. "Groundbreaking discovery in deadly childhood cancer." ScienceDaily. www.sciencedaily.com/releases/2013/12/131211131626.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) — An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins