黑料不打烊

鈥淲e undertook this study because we wanted to learn what was driving the growth of these tumours and how best to treat them,鈥� says the study鈥檚 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 黑料不打烊 University. 聽鈥淭his 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 tumour, moves us a little closer to that target.鈥�

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

For the study, the research team produced 鈥済enomic鈥� 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 鈥� a process involved in the early formation of an organ in an embryo 鈥� is somehow 鈥渉ijacked.鈥� 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.

鈥淕enomic approaches are offering unprecedented opportunities to understand cancer,鈥� explains co-principal investigator, Dr. Jacek Majewski, associate professor in the Department of Human Genetics at 黑料不打烊 University and a researcher at the 黑料不打烊 University and Genome Quebec Innovation Centre. 鈥淚n the past, researchers would meticulously follow individual genes and proteins to try to piece together what goes awry in a tumour. Today, we can rapidly look at the entire genome and, using computational analysis, identify the incorrectly produced genes 鈥� 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 tumour to a very promising target gene 鈥� DNMT3B.鈥�

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.

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

鈥淭his 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鈥檚 lives, and hopefully get more studies of its kind off the ground,鈥� states Andy Chabot, President and CEO of the Cancer Research Society.聽

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

About the study:

This work was supported by the Cancer Research Society.

Related links:

• Research Institute of the MUHC:
• The Montreal Children鈥檚 Hospital (MCH):
• 黑料不打烊 University: www.mcgill.ca
• The 黑料不打烊 University and G茅nome Qu茅bec Innovation Centre:
• SickKids:
• SickKids Research Institute, Huang Lab:
• Arthur and Sonia Labatt Brain Tumour Research Centre:
• Faculty of Medicine, University of Toronto:
• Garron Family Cancer Centre:
• Cancer Research Society: