Glioblastoma multiforme is one of the most aggressive tumor types of brain cancer. GBM (glioblastoma multiforme) is a very feared tumor. Dr. Anton Titov, MD. You have done some important work. You established a diagnostic criteria for GBM (glioblastoma multiforme) by molecular markers. These diagnostic markers affect GBM (glioblastoma multiforme) treatment for some patients. Dr. Anton Titov, MD. Please discuss your work in glioblastoma multiforme, GBM (glioblastoma multiforme). Dr. Sebastian Brandner, MD. Yes, you’re correct. Glioblastoma, GBM (glioblastoma multiforme), is the most aggressive brain tumor in adults. Glioblastoma is the most aggressive intrinsic brain tumor in adults. There is a diagnostic test that grew into the common clinical practice over the last 10 years. The GBM (glioblastoma multiforme) test result is important. This diagnostic test is done on the promoter of the gene called MGMT. Promoter is a region of the gene that drives the expression of the protein. The test measures whether this promoter of this gene is methylated. Methylation is little attachments to the promoter, to the DNA. So it’s actually not thе change in the DNA. Dr. Sebastian Brandner, MD. But it’s something that we call epigenetic change. So these little attachments are called “CPG islands”. They are methylated on the promoter. Sometimes you methylate the promoter. Then you essentially shut down the expression of this protein. So MGMT is actually a “DNA repair” enzyme. Sometimes you shut down the promoter of the DNA repair gene. Then it does not repair DNA anymore. So that’s bad generally, if damage to DNA repair gene happens in cancer tumors. But temozolomide is the medication that clinical teams are using to treat the glioma tumors. It is actually aims at destroying the DNA of these brain tumors. Temozolomide is a medication that cuts DNA in a tumor. So you have the DNA repair enzyme that tries to repair damage done by medication. But that’s not what we want. So that’s why those glioblastomas with a methylated MGMT promoter are better. Because there’s no more activity of the enzyme. Otherwise MGMT will repair tumor DNA. So tumor cannot repair itself. That’s why we do this methylation test. We did not establish the fact that MGMT methylation results in a better prognosis. It results in a better treatment response to temozolomide. Dr. Sebastian Brandner, MD. But we have established that diagnostic test as part of the common practice. We were one of the centers that started using a high throughput testing method. We are now able to offer the MGMT diagnostic test to many centers for a relatively affordable price. Especially to centers that see smaller number of these tumors. We pool glioblastoma tumor samples for this test. We scale up testing. That brings down the price. Price is for the benefit of the referring pathologist. It is for the benefit of the NHS and the patient. Obviously, in those glioblastoma brain tumor cases the patient’s treatment is affected. Dr. Anton Titov, MD. You can give patients a better estimate of prognosis. Leading brain tumor diagnosis expert explains how glioblastoma multiforme (GBM) molecular diagnosis is confirmed. Which mutations lead to brain cancer development?
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