Biol1020 Essay 18/3/12- Josiah Seto
A Major development into the cause of Brain Cancer in children
A recent breakthrough from a study on paediatric brain cancer, may be the key to finding a cure, or at least much more effective treatment. The study, spearheaded by the Research Institute of the McGill University Health revealed a significant genetic difference between this type of cancer and the adult equivalent
Brain cancer is one of the deadliest of cancers in children, and the most
common form of brain cancer, GBM multiforme has an average survival of only 12-17
months even with aggressive treatment.
As you may already know, cancer is a disease, which stems from damaged DNA, leading to uncontrolled cell division, and then tumours. Tumours, however, are not always cancerous, and are only malignant if they “invade nearby tissues and spread to other parts of the body” and may return even after being removed through surgical methods.
(National Institutes of
Brain cancer is particularly life threatening as it is located in an essential
organ of the body, which has limited space. The tumour in the brain may increase
the intracranial pressure, which leads to headaches, vomiting, comas, and in children;
large bulges in the fontanelles (soft spots which allow the skull flexibility
to fit through the birth canal). Other symptoms of brain tumours include many
neural dysfunctions ranging from impaired senses to changes in personality to
epileptic seizures, which sadly can be explained by many other diseases, and brain
cancer can be overlooked. (Charles Patrick Davis, 2012)
This study sequenced the exomes of 48 children who had GBM and found two genetic mutations which accounted for up to 40% of the GBM in the sample
An exome is a specific area of the entire genome which are important the
creation of particular types of proteins. This method is more efficient, as there
are over 180,000 exons in the entire genome, and the “relevant” exons can be
sequenced much faster and can detect variations or mutations much more
successfully (Sarah B. Ng, 2009).
Figure 1 MRI of a Glioblastoma multiforme
(Eric M. Thompson, 2011)
The two genetic mutations were:
1. “Somatic mutations in the H3.3-ATRX-DAXX chromatin remodelling pathway in 44% of the tumours”
(Jeremy Schwartzentruber, 2012)
2. “Recurrent mutations in H3F3A, which lead to amino acid substitutions in critical parts of the histone tail in 31% of tumours”
(Jeremy Schwartzentruber, 2012)
According to Dr Jabado of the MUHC, it was not known why children and adolescent GBM patients did not respond to treatments as well as adult patients. The commonplace treatments of chemotherapy and radiotherapy had inexplicably been resisted by tumours in children, which were revealed by this study to be caused by the mutations preventing the treatments to properly target and differentiate cancerous cells from healthy cells. He continued to say that this results “(are) significant here … (as) the first time in humans we have identified a mutation in one of the most important genes that regulates and protects our genetic information. This is the irrefutable proof that our genome, if modified, can lead to cancer and probably other diseases.”
Figure 2 Proportion of GBM patients with the Genetic mutation "H3F3A" in children, compared to adults
This genetic mutation has been detected in other forms of cancer, and the researchers from MUHC are hopeful that this breakthrough will lead to new treatments for cancer in specific patients with these mutations
(Hazell, 2012). Continued developments
such as these will lead to the future of patient care, which will utilise personalised
genome mapping and treatment plans based on the individual.
· Charles Patrick Davis, M. P. (2012). Brain Cancer. Retrieved Mar 18, 2012, from eMedicineHealth: http://www.medicinenet.com/brain_cancer/article.htm
· Eric M. Thompson, M. E. (2011, Jan 4). The paradoxical effect of bevacizumab in the therapy of malignant gliomas. Retrieved March 18, 2012, from Neurology: http://www.neurology.org/content/76/1/87/F4.large.jpg
· Hazell, K. (2012, Jan 31). Scientists Discover Genetic Mutation That Causes Brain Cancer In Children. Retrieved March 18, 2012, from Huffinton Post: http://www.huffingtonpost.co.uk/2012/01/31/genetic-mutation-causes-brain-cancer-children_n_1244187.html
· Jeremy Schwartzentruber, A. K.-Y.-A.-B. (2012). Driver mutations in histone H3.3 and chromatin remodelling genes in paediatric glioblastoma. Nature , 7.
· National Institutes of Health. (2012, Feb 6). What is Cancer. Retrieved May 18, 2012, from National Cancer Institute: http://cancer.gov/cancertopics/cancerlibrary/what-is-cancer
· Sarah B. Ng, E. H. (2009). Targeted capture and massively parallel sequencing of 12 human exomes. Nature .
· Science Daily. (2012, Jan 30). Genetic Breakthrough for Brain Cancer in Children. Retrieved March 18, 2012, from Science Daily: http://www.sciencedaily.com/releases/2012/01/120130102522.htm