Genomic Testing and 2021 World Health Organization Glioblastoma Classification
The definition of glioblastoma has changed greatly over the last several years. Most notably, Genomic Testing can now be used to help diagnose glioblastoma.
What is glioblastoma?
Glioblastoma is the most common malignant brain tumor that arises in the brain. It is also the most aggressive. It is a type of glioma, a type of brain cancer that arise from the glial cells in the brain. Its designation as Grade 4 indicates that it is in the highest and most malignant grade of gliomas.
Glioblastomas are highly aggressive and challenging to treat. They tend to invade surrounding healthy tissue, which can make it difficult to define clear tumor borders during surgical removal. As research has evolved, doctors and scientists are understanding more about the unique molecular machinery that makes glioblastoma particularly aggressive, and more will certainly be discovered in years to come with increased genomic testing, like that soon to be offered by the Glioblastoma Foundation.
Using Genomic Testing to Classify Glioblastoma
The World Health Organization (WHO) publishes the most widely accepted classification system for brain and spine tumors. This system contains the criteria that physicians use to diagnose and categorize different types of tumors.
Historically, glioblastomas have been classified by examining their appearance under a microscope, a process known as histopathology. Doctors checked for specific visual features like abnormal cell size and shape, high rates of cell division, and dead tissue inside the tumor.
In 2021, the WHO updated its classification system, bringing significant changes to how we diagnose and categorize glioblastoma. This classification system looks at specific alterations in the DNA of glioblastoma tumors to identify genetic mutations and alterations that drive glioblastoma growth and aggressiveness.
Genomic Testing and 2021 WHO Classification of Glioblastoma
The 2021 WHO classification system made two key changes to the criteria used to diagnose glioblastoma. Let’s explore each of these changes and how they are affecting clinical care for glioblastoma today.
1. IDH-Wildtype Status
To classify a tumor as glioblastoma, doctors check whether there are no changes in the DNA sequence of a gene called isocitrate dehydrogenase (IDH).
Many brain tumors have mutations in their IDH genes, and these tumors tend to be less aggressive and respond better to treatment than tumors without any IDH mutations. Previously, glioblastomas included tumors both with and without IDH-mutations. However, further research revealed that IDH-mutant tumors behave very differently from most glioblastomas.
As of 2021, the name glioblastoma is only given to tumors that with unmutated, or ‘wildtype’ IDH genes. By incorporating IDH wildtype status and other key genetic differences, 2021 WHO classification system more accurately reflects the underlying molecular machinery that makes glioblastoma different from cancer types. This can help doctors determine prognosis and assess treatment options.
2. Visual and/or Molecular Features
Previously, doctors looked for certain histopathological features to identify a tumor as a glioblastoma, such as necrosis (areas of dying cells within the tumor) or microvascular proliferation (abnormally shaped blood veseels in the tumor.) Now, glioblastoma can be diagnosed if a tumor has one of the following three genomic alterations, even without its classic visual features.
- TERT promoter mutation: A genetic change that helps tumor cells grow indefinitely
- Chromosome 7 gain/chromosome 10 loss (+7/-10): A genetic alteration where chromosome 7 is gained and chromosome 10 is lost
- EGFR amplification: An increase in the number of EGFR (epidermal growth factor receptor) genes, which can drive uncontrolled tumor cell growth
The Promise of Genomic Testing
We’re proud to usher in a new era of genomic testing at the Glioblastoma Foundation. These state-of-the art genomic tests will not only help us diagnose glioblastoma more accurately, but also allow us to identify the best targeted treatments for each patient's glioblastoma tumor.
The 2021 WHO classification system takes significant strides forward in diagnosing glioblastoma by incorporating molecular criteria. It emphasizes genetic alterations such as IDH-wildtype status and specific genomic features alongside visual characteristics. This helps ensure that the diagnosis reflects the tumor’s underlying biology, improving prognostic accuracy and guiding tailored treatment approaches.
This updated classification emphasizes the importance of integrating molecular features into the management of brain tumors, especially glioblastoma. The molecular information obtained from genomic testing will become more and more important in the coming years, and will allow us to unlock new insights into diagnosing and treating glioblastoma tumors effectively.
Click here to learn more about our new Genomic Testing and Research Laboratory, opening soon, in Durham, NC.
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