According to the National Brain Tumor Society (NBTS), nearly 700,000 people in the United States are living with a brain tumor that has yet to be diagnosed and treated. Most patients undergo a variety of treatments, as it is very unlikely to treat this disease using only one form of treatment. Patients can opt to undergo specialized therapies: radiation: in the form of radiation and x-rays that attempt to destroy the tumor cells in the body, chemotherapy: in the form of drugs and chemicals that are used to destroy dividing tumor cells, target therapy: which focuses on disrupting or altering certain molecules or pathways that are required for tumor cell growth, and tumor-treating field therapy: wearable device that exerts an electric field that disrupts the cell division via electrical charge inside tumor cells. Very commonly, patients may decide to undergo surgery to remove the tumor. However it is very difficult to completely remove a brain tumor since there is a high risk of developing a recurring tumor due to presence of the residual tumor and cells from the primary tumor. Despite these treatment options, the NBTS reports that over 16,500 people will still die from a malignant brain tumor this year.
Glioblastoma Multiforme (GBM) is the deadliest form of brain cancer. The deadly tumor arises from glial cells, which are star-shaped cells that serve to support and maintain healthy nerve cells located in the brain. The survival rate for glioblastoma patients is very small in comparison to other types of brain cancers, such as lower-stage astrocytoma or oligodendroglioma. According to NBTS, the survival rate percentage of people who lived at least five years after being diagnosed with GBM was 5.1%. According the American Cancer Society (ACS), the five-year survival rate for adults diagnosed with GBM estimates to about 8%. Although the disease is not as common as lung, colorectal or breast cancer, it has the same lethal capacity of destroying one of the most vital and functional organs in the body. Diagnosis and advanced biotechnology can have the capability of helping save lives and prevent people from developing GBM.
Currently, there are several ways of diagnosing potential GBM patients. Standardly, neurological exams are carried out on the patients to detect visible signs of impairments in vision, hearing and movement. Movement coordination and reflexes are examined to determine whether the nervous system is properly functioning, since they are essentially all signals from the brain. Brain imaging technology, such as computer tomography (CT) and magnetic resonance imaging (MRI) are utilized to detect tumor formations in the brain. Positron emission tomography (PET scan) can be used to detect the presence of GBM as well. Aside from imaging technology, biopsies of suspected masses or tissue can be done, and the extraction of cerebrospinal fluid. Both samples can be used to observe unusual and abnormal pathological characteristics. Determining the presence of GBM is helpful in having the premature disease treated and cleared as soon as possible. However, if we are able to pinpoint specific genes in humans that predispose to GBM is there a way we can try to eliminate GBM completely?
This study concentrates on understanding which genes predispose to GBM. According to Urbanska et al. (2014) GBM is often spontaneously developed in patients, although there have been familial cases recorded. Most of these familial cases show a history of GBM in ancestry that is believed to be passed onto their children and grandchildren. For all we may know, a person with familial history of GBM may have genetic predisposition to the disease and not even know about it nor expect it. Understanding these familial cases and the genetic differences in GBM affected patients, we may be able to pinpoint GBM-related genes. Utilizing knowledge and data from several publications on GBM patients, we will be observing whether the presence of variations in certain genes are linked to GBM.
To understand whether these genes truly have a role towards GBM formation, a model organism, Caenorhabditis elegans(C.elegans) will be used to observe the impact of the knock-out of specific genes. C.elegansis a roundworm or nematode that is commonly used for genetic and reproductive research. Using this organism allows us to understand the effect of the gene knockout based on the possible adverse effects it has on the reproductive and general nervous and muscular system of the nematode. C.elegansis practically a microscopic organism with a simple anatomy, which advantageously consists of a nervous system and structure that serves as a brain called the neural tube. If the genes that we observe truly cause physical and reproductive alterations to the organism, then staining microscopy will be used to better understand the cellular and molecular changes of the organism. In this study, we would like to understand what changes are applied to the glial cells that are present in C.elegans.
The genetics behind GBM are understudied and therefore is a lack of effective GBM-specialized target therapy. Understanding and confirming these changes in a model organism will allow us to apply the knowledge from this study to help improve GBM predisposition technology and target therapy that can be used to treat people that are in danger of developing this disease. More people consider undergoing genetic testing to find out whether they are prone to developing a genetically-related disease and adding new information to the screening panel can be very beneficial.