‘Fingerprinting brain tumors’. Brain cancer molecular diagnosis. 7
Another type of brain tumor is the IDH-mutant tumor. Anaplastic oligoastrocytoma (AOA) does not have that nuclear protein loss. Anaplastic oligodendroglioma (AOD) brain tumor normally has the 1p/19q chromosomal co-deletion. Dr. Anton Titov, MD. So that is a co-deletion that leads to very specific loss of one chromosome arm at 1p and at 19q. This can only be detected with real molecular techniques. Dr. Sebastian Brandner, MD. A little tag is put onto these chromosomes. The number of tags are counted in the brain tumor tissue. So if one has 100 cells, and if there are only 50 tags, that means that the other 50 chromosome parts are lost. That’s a “1p loss”, for example. Dr. Sebastian Brandner, MD. We have slightly different way of testing. We scrape off the whole brain tumor tissue. We do a “quantitative PCR”. Dr. Anton Titov, MD. This means we can detect whether it’s one or two copies of chromosomes. Now, that is sufficient in most of these type of brain tumors. Then there are a large number of more rare brain tumors. These tumors are anaplastic oligodendroglioma (AOD) and Anaplastic oligoastrocytomas (AOA). They might be benign or malignant. They are really difficult to diagnose. Sometimes we are really at a loss of what these brain tumors are. There is a 4th generation of molecular diagnostics. It’s based on a feature that happens to the DNA of the tumor cells. Sometimes cells become malignant. I mentioned earlier that MGMT promoter becomes methylated. That happens not only to the MGMT promoter. Anaplastic oligoastrocytomas (AOA) actually is rare. It happens throughout the genome. So this methylation is a biological mechanism by which cell can be switched on. Or Anaplastic oligodendroglioma (AOD) cell growth can be switched on. Or it can be switched off. Certain cell features can be promoted or can be silenced. Sometimes the cell or tissue turns malignant. Dr. Sebastian Brandner, MD. The pattern where these methylation tags are present [methylation pattern] changes around in the brain tumor genome. These changes can be picked up by a microarray. It is a gene array looking at nearly 1 million different points across the whole genome. The team at Heidelberg University has developed an algorithm. We are allowed to use it. We can now extract the brain tumor DNA. We can put Anaplastic oligodendroglioma (AOD) on a chip. That’s done at our local genomics facility. Then we upload the whole data information. It’s just a few megabytes of information. that represents just under a million different data points across the whole brain tumor genome. It is not only a “fingerprint”. It is a “retinal scan” of the Anaplastic oligoastrocytomas (AOA) brain tumor. Dr. Anton Titov, MD. Well, you can actually call it a fingerprint. I think fingerprints is a very good comparison of brain tumor molecular diagnosis. Each brain tumor has its own fingerprint. Only certain type of tumors have fingerprint features that are common in all similar type of brain tumors. But there’s the archive of 10,000 of these brain tumors. Each group has about 20 – 30 – 40 tumors. Then the new brain tumor that we are having here. We are having problems with diagnosing Anaplastic oligoastrocytomas (AOA). It is compared against the database. Then there is a mathematical algorithm that tells you exactly which class of tumors this new brain tumor is likely to belong. Dr. Anton Titov, MD. The report looks like this. What you see here is actually not the classification. But this shows you how the tumor genome looks. Dr. Sebastian Brandner, MD. This is the genome. This is a chromosome 1. This is chromosome 22. You can see that this gene profile is enhanced. It is amplified. More chromosome copies are present. This pattern is a characteristic pattern of glioblastoma. Leading brain tumor diagnosis expert discusses precise diagnosis of gliomas. Oligodendroglioma and glioblastoma multiforme (GBM). How mutation analysis helps to predict prognosis and treatment result in gliomas?
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