Methylation: The Cause of Brain Tumor?

When one thinks of the word “cancer” breast cancer, lung cancer, and skin cancer are among the various types that first come to mind. One type of cancer that is often neglected is Brain Tumor. According to the National Tumor Society, more than 500 people per day are diagnosed with primary or metastatic brain tumorand what’s worse is that the mortality rates for those diagnosed with brain and nervous system tumors haven’t improved over the past decade. The desperate need for new treatments and therapies for brain tumor is evident and it is the hope of many people whose loved one have suffered the wrath of this incurable disease that 2011 will bring new treatments and bring the path to the cure closer than ever before [1].

Neuroscience is an area of science that has faced its fair share of failures, yet that doesn’t mean scientists should give up on the field itself. Recently, researchers at the Alpert Medical School made an important discovery that may change the face of brain tumor treatments and diagnosis forever.

This new discovery is developed from the hypothesis that a relationship exists between mutations in tumors and methylation patterns found in their genomes (2). Chemically speaking, methylation is the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. When DNA is methylated, gene silencing often occurs which could be the cause of the tumor. Gene silencing is a process of gene regulation which “switches off” a gene through a mechanism. Researchers and neuroscientists speculate that the methylated regions mark the genes involved in metabolic processes which explain the abnormal behavior of tumor cells [2]

Brooke Christiansen, a Brown post-doctoral research associate conducted a study using the Illumina GoldenGate methylation array. The research associate speculated that brain tumors specifically dealt with the IDH gene, an enzyme that is involved in glucose sensing which is an important aspect for metabolic processing. The study found that brain tumor patients with the IDH gene survive longer than those without the mutation. The reason behind this is unknown, however pharmaceutical companies are trying to develop  a drug that inhibits the process of methylation. If such a drug is developed, then perhaps the cell will return to its normal state instead of undergoing methylation. Christiansen’s research may be a medical breakthrough however his hypothesis’ have a long way to go until they can be considered true. An immediate result of his research is that IDH mutation can be measured clinically [2].

The National Cancer Society has recently conducted similar research on a type of brain tumor common in children called medulloblastoma. Similar to Christiansen’s research, researchers such as Dr. Victor Velculescu of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center discovered that some tumors harbored previously unknown mutations in the genes MLL2 and MLL3. These genes are involved in histone methylation, an epigenetic process that affects the structure of chromatin and the regulation of other genes. While the drug that inhibits methylation hasn’t been discovered yet, an experimental drug called GDC-0449, which inhibits the hedgehog signaling pathway, is being evaluated in children with recurrent medulloblastoma [3].

“Right now, there is hope and excitement that we may have new therapies to introduce for these patients,” said Dr. Amar Gajjar of St. Jude, who is leading ongoing NCI-sponsored trials with the drug on behalf of the Pediatric Brain Tumor Consortium [3].

Brain tumor may not be the first thing on the minds of people when they hear the word cancer, however it is one of the most vigorous and brutal forms of cancer. Almost every single patient with an inoperable tumor dies within a 5 year set time interval after diagnosis. However, with the new studies being conducted on histone methylation and developing a drug that inhibits this epigenetic process, the cure for brain tumor isn’t far away.  Furthermore, the studies that have already been conducted in the pediatric field dealing with medulloblastoma can prove to be helpful in developing a way to inhibit methylation. The cure to brain tumor is in sight, however there is still a long way to go in curing one of the most deadliest disease in the world.

When one thinks of the word “cancer” breast cancer, lung cancer, and skin cancer are among the various types that first come to mind. One type of cancer that is often neglected is Brain Tumor. According to the National Tumor Society, more than 500 people per day are diagnosed with primary or metastatic brain tumorand what’s worse is that the mortality rates for those diagnosed with brain and nervous system tumors haven’t improved over the past decade. The desperate need for new treatments and therapies for brain tumor is evident and it is the hope of many people whose loved one have suffered the wrath of this incurable disease that 2011 will bring new treatments and bring the path to the cure closer than ever before [1].

Neuroscience is an area of science that has faced its fair share of failures, yet that doesn’t mean scientists should give up on the field itself. Recently, researchers at the Alpert Medical School made an important discovery that may change the face of brain tumor treatments and diagnosis forever.

This new discovery is developed from the hypothesis that a relationship exists between mutations in tumors and methylation patterns found in their genomes (2). Chemically speaking, methylation is the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. When DNA is methylated, gene silencing often occurs which could be the cause of the tumor. Gene silencing is a process of gene regulation which “switches off” a gene through a mechanism. Researchers and neuroscientists speculate that the methylated regions mark the genes involved in metabolic processes which explain the abnormal behavior of tumor cells [2]

Brooke Christiansen, a Brown post-doctoral research associate conducted a study using the Illumina GoldenGate methylation array. The research associate speculated that brain tumors specifically dealt with the IDH gene, an enzyme that is involved in glucose sensing which is an important aspect for metabolic processing. The study found that brain tumor patients with the IDH gene survive longer than those without the mutation. The reason behind this is unknown, however pharmaceutical companies are trying to develop  a drug that inhibits the process of methylation. If such a drug is developed, then perhaps the cell will return to its normal state instead of undergoing methylation. Christiansen’s research may be a medical breakthrough however his hypothesis’ have a long way to go until they can be considered true. An immediate result of his research is that IDH mutation can be measured clinically [2].

The National Cancer Society has recently conducted similar research on a type of brain tumor common in children called medulloblastoma. Similar to Christiansen’s research, researchers such as Dr. Victor Velculescu of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center discovered that some tumors harbored previously unknown mutations in the genes MLL2 and MLL3. These genes are involved in histone methylation, an epigenetic process that affects the structure of chromatin and the regulation of other genes. While the drug that inhibits methylation hasn’t been discovered yet, an experimental drug called GDC-0449, which inhibits the hedgehog signaling pathway, is being evaluated in children with recurrent medulloblastoma [3].

“Right now, there is hope and excitement that we may have new therapies to introduce for these patients,” said Dr. Amar Gajjar of St. Jude, who is leading ongoing NCI-sponsored trials with the drug on behalf of the Pediatric Brain Tumor Consortium [3].

Brain tumor may not be the first thing on the minds of people when they hear the word cancer, however it is one of the most vigorous and brutal forms of cancer. Almost every single patient with an inoperable tumor dies within a 5 year set time interval after diagnosis. However, with the new studies being conducted on histone methylation and developing a drug that inhibits this epigenetic process, the cure for brain tumor isn’t far away.  Furthermore, the studies that have already been conducted in the pediatric field dealing with medulloblastoma can prove to be helpful in developing a way to inhibit methylation. The cure to brain tumor is in sight, however there is still a long way to go in curing one of the most deadliest disease in the world.

References

  1. http://presszoom.com/story_164408.html
  2. Villacorta, Natalie. Tumor Research Could Lead to Treatment Breakthrough. http://www.browndailyherald.com/mobile/tumor-research-could-lead-to-treatment-breakthrough-1.2450647
  3. Seeking Better Treaments for Brain Tumors in Children <http://www.cancer.gov/ncicancerbulletin/012511/page6>.

Written by The Triple Helix at Ohio State University

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