Gliomas

Dr. Prem Pillay , Singapore Brain Spine Nerves Center, Singapore

Senior Consultant Neurosurgeon with super speciality training in Neurosurgical Oncology

(Fellow at MD Anderson Cancer Center and Hospital, U of Texas, USA)

What are Gliomas?

Gliomas are a category of primary brain tumours that arise from glial cells, which provide support and insulation to neurons in the central nervous system. These tumours can occur in both the brain and spinal cord and are classified based on the type of glial cells involved. Gliomas are the most common type of brain tumour in adults and can range from slow-growing to highly aggressive forms.

Glioma and Glioblastoma: Advances in Classification and Research

In the United States, an estimated 17,000 adults will be diagnosed this year with diffuse glioma, which includes glioblastoma, astrocytoma, and oligodendroglioma. Among these, high-grade gliomas like glioblastoma have worse prognoses.

Glioblastoma is classified based on its histological characteristics (left) as well as IDH status.

“For many years, the Neuro Oncology community has observed significant variation in survival even within traditional classification groups,” said Dr Prem Pillay from the Singapore Brain Spine Nerves Center.“This was an enormous impetus for researchers to find new markers to better characterize glioma subtypes.”

In 2015, two landmark publications, including one from a team of UCSF researchers, found three new tumor markers that reliably classified glioma patients into distinct groups with notable differences in survival, age at diagnosis, among others.² ³

2016 World Health Organisation (WHO) Classification Update

In 2016, the WHO reorganized their classification system for adult diffuse glioma to integrate those molecular features, in addition to others identified since then.

The majority of adult diffuse glioma are now classified into the following five groups:

1. Glioblastoma, IDH wildtype (no mutation)

2. Glioblastoma, IDH mutation

3. Diffuse or anaplastic astrocytoma, IDH wildtype (no mutation)

4. Diffuse or anaplastic astrocytoma, IDH mutation

5. Oligodendroglioma or anaplastic oligodendroglioma, IDH mutation with 1p19q co-deletion

   
   

Categorization of adult diffuse glioma, along with characteristics for each of the five subtypes.Image credit: Figure 1 from Molinaro et al. (2019).

“By better understanding glioma subtypes, we can help our patients make decisions about treatment,” said Dr Prem Pillay

The Future of Brain Tumor Classification

Since then, additional markers have been identified and are in use today to further improve accuracy in prognoses for certain gliomas. A comprehensive overview of molecular features that are also associated with patient outcome and/or treatment response includes the following:

• TERT and ATRX mutations affecting telomere maintenance

• Tumor methylation profile

• Methylation of the MGMT promoter

• CDKN2A and/or CDKN2B deletion

• H3 K27M mutation

  
  

In the last decade, identifying such molecular features and their associated pathways has provided mechanistic insight into how these distinct tumor subtypes form and their potential response to targeted therapy. For instance, researchers recently identified a protein subunit that activates mutated TERT promoters, which is currently under investigation as a potential therapeutic target.

As we continue to identify additional markers, proposed changes to the WHO guidelines remains an ongoing topic of discussion. The cIMPACT-NOW (the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy), was created to assess and recommend regular updates to the brain tumor classification system.

The discovery of molecular features to better characterize glioma subtypes has certainly impacted the clinic and continues to shape the direction of research.

“Increasingly, molecular analysis of patient samples is becoming a more widespread practice. Identifying a patient’s unique tumor profile is critical not only for diagnosis and prediction of prognoses, but potentially for tailoring treatment to the patient’s specific gene alterations”

Identifying Glioma Risk Factors

Another recent, significant advance in brain tumor research involves the discovery of 25 inherited variants that increase the risk of glioma. The majority of these gene alterations are either in or near genes known to be involved in specific cancer-related pathways, providing additional insight into how gliomas develop.

In contrast, recent observations suggest that a history of allergies (or other conditions with heightened immune responses, like asthma and eczema) is associated with decreased glioma risk. These findings have spurred additional research into characteristics of the immune system that are involved in glioma pathogenesis and prognosis.

Large-scale retrospective and prospective epidemiological studies to characterize peripheral immune profiles on the basis of archival DNA are underway at UCSF to assess how variation amongst patients’ immune profiles impacts glioma risk.

Together, these findings combined with the discoveries of changes within the tumors provide a solid foundation for future research into why some people get glioma and what may be done to help reduce the risk of disease or death from this disease.

Conclusion

Gliomas are a complex group of brain tumours that require specialised and multidisciplinary care. Early diagnosis and tailored treatment can significantly improve outcomes and quality of life. At Singapore Brain Spine Nerves Center, we are dedicated to providing expert care for glioma patients, leveraging advanced diagnostic and treatment options. If you or a loved one are experiencing concerning neurological symptoms, schedule a consultation today for comprehensive evaluation and guidance.

References:

• UCSF Brain Tumor Information

• Cleveland Clinic Brain Tumor Information

• Singapore Brain Spine Nerves Center