A Major development into the cause of Brain Cancer in children

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 (Jeremy Schwartzentruber, 2012). 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 Health, 2012). 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 (Science Daily, 2012). 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.” (Science Daily, 2012)

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.

Genetics in Cancer

Genetics in Cancer

Hello, everyone. Today, I shall discuss the topic of cancer or, more accurately, a recent advance in genetics that should assist us greatly in the fight against cancer. Cancer currently afflicts 112,300 Australians, and causes 39,000 deaths every year (Australian Institute of Health and Welfare 2008). You can see that this is quite an intolerably large figure. Luckily, scientists are becoming able to identify the specific genetic mutations that lead to individual malignant neoplasms (that’s just the smart-people name for cancerous tumours). This innovation lets us give more effective treatment, and undergo greater in-depth analysis of the origins of a cancer.


The University of Colorado

This technique is still in the early stages of development, so scientists are not even close to identifying all of the genetic mutations that cause all types of cancer. However, researchers at the University of Colorado Cancer Centre performed a clinical trial in 2010 in which they did actually manage to link genetic anomalies to cancer. In this case, they studied a particular rearrangement of genes inside the cancer cells of thirteen different lung cancer patients. The study involved testing a drug designed to target this ‘gene rearrangement’ (Camidge 2010).

Diagram of human lungs containing a tumour

These researches managed to show that the identification of genetic mutations in cancer cells allows cancer to be treated very effectively. To see just how effective it is, you can look at the results of the trial for one of its patients, 60-year-old Ellen Pulhamus. Before the study, she had five malignant tumours, which shrunk by 62 percent after just six weeks! In addition to that, another round of treatment brought down their size by a further 50 percent! (Brown 2010) Results as fantastic as these mean that oncologists should soon be able to move on from prescribing drugs that will only work for about one in ten cancer patients, and charge forward to the stage where they can determine exactly which patients will benefit from which treatments, by looking at the genes of their tumours (Brown 2010).


Tumours in a lung


Another goal of the researchers in this field is to try to use gene identification to trace cancer cell mutation back to its origins. This could allow the primary prevention of some cancers by exposing the kinds of lifestyles and environmental conditions that lead to them (Brown 2010). It may even provide current cancer patients with some peace of mind, in that they could find out the reason or reasons behind them being so sick.




Cancer is a tragedy that most of us will have to experience at some point in our lives, whether it be through having to endure it ourselves or witness it in someone close to us. The work done by researchers like those at the University of Colorado Cancer Centre will allow us to extend, or even save, a considerable number of lives, from within our species and perhaps outside it. With cancer being the prevalent calamity that it is, such an achievement will have far-reaching positive consequences for our entire race.

Alcoholism - Is it a Genetic Mutation?

Alcoholism - Is it a Genetic Mutation?


Alcohol dependence, also known as alcoholism, is considered medically as a disease. Its symptoms, as listed by the American Association for Clinical Chemistry (2010), include increased tolerance, cravings, loss of control and physical dependence. For decades, sufferers of the disease have not only experienced its harsh physical and psychological effects, but also discrimination and stereotypes created by society. In recent years, however, scientific research has revealed that the likelihood of developing alcoholism is increased by the possession of variations in certain genes (Arbor 2011). When variation occurs in two specific genes, unc-79 and GABRA2, it is thought that it influences alcohol sensitivity (O’brien 2010) and impulsive behaviours (Arbor 2011).

 Gene mutations are permanent alterations to sequences of DNA sections of chromosomes (U.S. National Library of Medicine 2012). When mutations occur in genes, it can affect the cell or organism’s ability to function normal, therefore promoting alcoholism in humans.

The gene unc-79 in mice, as well as the human version of the gene, is a poorly understood gene thought to interact with a neuron called NALCN (O’Brien 2010). In studies with mice, the mice that possessed mutated unc-79 genes voluntarily chose alcohol over water when offered the two. The mutant mice also were highly more sensitive to the alcohol. When injected with pure ethanol, the mice blacked out for much longer than the non-mutant mice. These observations in mice are thought to arise from the unc-79 gene mutation, dubbed as Lightweight, altering the neuronal responses to alcohol governed by NALCN (O’Brien 2010).



The GABRA2 gene is responsible for the functioning of receptors in part of the mammalian brain called the insula (Arbor 2011). In a recent study, those with the variant GABRA2 gene demonstrated higher levels of impulsiveness when under distress, with high activation in the insula. This links to the idea humans, particularly females, turn to alcohol to relieve distress and anxiety (Arbor 2011).

Both unc-79 and GABRA2 gene variants are just some of the genes that contribute to the symptoms of alcoholism, but do not directly cause it. However, as alcoholics, their families and researchers attempt to discover its medical foundations, the discoveries of mutations in genes as alcoholism contributors is extremely significant for prevention, treatment and understanding of alcohol dependence.

DNA as a Data Storage Device

DNA as a Data Storage Device

In this day and age, we are all surrounded by technology, with gadgets and gizmos such as CDs, iPods, phones, computers, USBs – all driving us towards the ongoing quest for new and better ways to store information. With the past few years, scientists have been investigating every possibility, ranging from semiconductors to carbon “nanoballs” to even our very own DNA!
Deoxyribonucleic acid, or DNA, possesses many ideal characteristics of a data storage device for the future. Present in all living organisms, a key feature of DNA is its capacity to store significantly large amounts of information in its nucleotide sequences. The structure of a nucleotide consists of a sugar-phosphate backbone, attached to one of the four nitrogenous bases – Adenine, Thymine, Cytosine and Guanine.
Figure 1: The structure of a nucleotide, consisting of a phosphate group, deoxyribose (sugar) and a nitrogenous base.

Using genome sequencing, these nucleotides can be connected to form synthetic oligonucleotide sequences containing data stored in the form of specifically ordered nitrogenous bases.
In a recent study conducted by Yachie et al. (2007) at Keio University, the practicality of using bacterial DNA for long-term, large-volume data storage was investigated. The researchers were able to store a short, alphanumeric message in the loci of a Bacillus subtilis genome and retrieve it successfully. To do so, their chosen message “E=mc2” was firstly translated into dinucleotides, using a 4-bit binary code encryption key.
Figure 2: Encryption keys used in the Yachie et. al (2007) study at Keio University, Japan.

These dinucleotides were then used to form long sequences that were then injected into the Bacillus subtilis cells. After an overnight incubation period, the data was then recovered.
Figure 3: The 4-bit binary codes translate into dinucleotides which make up synthetic oligonucleotide sequences.

 The most common data storage and recovery method for DNA is based on polymerase chain reaction (PCR), which involves the use of primers to amplify the coded regions of DNA. Encryption keys are then employed to decode each dinucleotide into its corresponding bit code and if necessary, into alphanumeric code for convenient use or interpretation.
Figure 4: Bacillus subtilis under a microscopic.

Not only can DNA significantly more bytes than our currently existing mechanisms, but it is also praised for its extreme durability in long-term data storage. Naturally, DNA is passed down from generation to generation of living organisms, and because of this, scientists postulate that any data inserted in an organism’s genome will last as long as the line of the host organism, which is often hundreds of thousands of years. 
However, if the organism undergoes genetic evolution or adaptation, there are several problems that may occur, including data transmutation or loss. Several methods have been suggested to reduce the effect of these mutation rates, such as the selection of a robust host organism that can survive in harsh environments. In addition, the study by Yachie et al. (2007) suggests storing the data in an “alignment-based” method, where several back-ups of the data are also inserted with the original information to increase the stability of DNA data and reduce the chances of data deletion.
The phenomenon of using genomic DNA to archive information is considered as a significant advancement in genetics. According to recent studies, the natural characteristics of DNA, such as compactness, heritability and durability construct it as an ideal data storage device – which may ultimately blur the line between nature and technology forever.

Can't stop eating? Blame it on your genes

Can't stop eating? Blame it on your genes

Obesity is a medical condition where excess body fat accumulates to the extent of causing adverse effect on health which may lead to reduced life expectancy with increased health problems. It increases the likelihood of different diseases especially the heart disease, cancer as well as type two diabetes. Obesity tends to run in families. Weights of adults selected during studies reveal that their weights are closer to their biological parents’ weights.
A recent study done by Guey-Ying Liao and his colleagues (2012) suggests that human obesity may possibly be caused by mutations in the Bdnf gene as it produces transcripts having either short or long 3’ un translated regions (3’ UTRs). However, in regulation of energy balance, the precise role of brain-derived neurotrophic factor (BDNF) is unknown. The relationship between Bdnf mRNA with along 3’ UTR which means long 3’ UTR Bdnf mRNA, leptin neural activation and the body weight is shown. Long 3’ UTR Bdnf mRNA has been found to be enriched in dendrites of hypothalamic neurons. It has also been found that insulin and leptin could possibly stimulate its translation in dendrites.
Mice harboring a truncated long Bdnf 3’ UTR furthermore developed acute hyperphagic obesity. However, this was completely reversed by viral expression of somewhat long 3’ UTR Bdnf mRNA found in the hypothalamus. The ability of leptin in activating hypothalamic neurons and inhibiting food intake was compromised despite the presence of leptin receptors, in the mice. The results obtained revealed a novel mechanism which linked leptin action to BDNF expression happening during hypothalamic mediated body weight regulation and this also implicated dentritic protein synthesis in the process.
Researchers claim to have found a single mutant gene is the one to blame for the inability of brain to tell obese people when to stop eating. The brain derived neurotrophic factor in mice either stops or slows passage of leptin as well as the insulin signals through the brain. In the humans the aforementioned hormones are released at somewhere at the time when one can see the bottom of the colonel’s sixteen piece bucket. It is not usually the guiltiness that tells one to stop but the brain dictates when the climax is reached. In cases where the signals fail to reach the locations that are of concern in the area in brain signaling satiety.
Such discovery may possibly open up novel strategies which help the brain control body weight. The Bdnf does not only control body weight, but notably in failure to development of one of Bdnf gene, there is a flow effect resulting in deficits in learning and memory in mice. Neurons rarely talk to each other in case there is a problem with Bdnf gene and as such, the leptin and insulin signals become effective without modification of appetite. Faulty transmission line can be repaired by the strategy where missing Bdnf would be produced using virus based gene therapy despite the difficult of delivering across the brain blood barrier.
 

The lack of a single gene has been found to cause obesity. Leptin appears linked to human disease in which case several childhood diseases have been associated with mutations in leptin genes. Leptin however plays a big role in the body of human beings today. As an issue of concern in human science, research findings should be well administered so as to ensure that the risks of obesity associated with gene mutations are effectively curbed.