Methylation Program: Methylation Profiling Program of CNS Tumours
What is DNA Methylation?
DNA methylation has an important implication in the understanding of cancer formation and progression. The tight regulation of DNA methylation patterns is disrupted in cancer and these typically result in the inactivation of tumour suppressor genes and activation of oncogenes. These aberrant gene expression profiles drive many pro-oncogenic abilities and characteristics such as increased cell proliferation, cell motility, matrix degradation, immune system evasion, and the capability to metastasize.
Recently, the study of DNA methylation has been adapted to the field of neuro-oncology. Brain tumours are a heterogeneous disease group and the specificity of whole-genome DNA methylation patterns provide a more objective means to resolve diagnostic ambiguities based on traditional histopathological criteria and routine molecular tests. Furthermore, DNA methylation provides a tool for potential identification of biologic tumour subtypes and more accurate prediction of tumour behaviour and treatment response. Application of whole-genome DNA methylation profiling (MP) to Central Nervous System (CNS) tumours will result in better diagnostic accuracy, prediction of tumor course outcome, and response to treatment (Capper et al. 2018).
How has the Zadeh lab innovatively used this method for profiling CNS tumours?
Dr. Gelareh Zadeh’s research laboratory has established the expertise in whole-genome methylation profiling of CNS neoplasms. The laboratory is located in the MacFeeters Hamilton Centre for Neuro-oncology Research at the Princess Margaret Cancer Center, and the team actively investigate the DNA methylation signatures of a wide range of the most common primary and metastatic brain tumours. To facilitate high-throughput processing of these tumour samples for methylation profiling, we have established a robust standardized workflow for DNA methylation in research projects and for methylation profiling diagnostically challenging CNS tumors using DKFZ CNS tumour classifier.
Methylation profiling of meningioma to predict tumour recurrence.
Meningiomas are the most common primary brain tumour. Often, these tumours can be cured with surgery alone. However, there remains a risk for tumour regrowth (recurrence) that cannot be reliably predicted using standard pathology alone. Our lab has performed methylation profiling of a large number of meningiomas from multiple institutions around the world. We have developed and streamlined artificial intelligence algorithms to predict the risk for tumour regrowth (recurrence) for an individual patient using the methylation signature of the patients tumour in combination with standard clinical factors such as the WHO Grade of the tumour and the extent of resection at surgery (Simpson grade). This study is a major landmark in brain tumour practice, as it is the first predictor of outcome that has been used in clinical practice with high reliability. The predictor facilitates decision making regarding the need for radiation therapy following surgical resection of patients with high-risk for recurrence. For the scientific background and interpretation of the data using the meningioma predictor, please see Nassiri et al. (2019) paper titled “DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management.”
To determine the methylation profile and recurrence score for your tumour, your physician is required to send the tumour samples to our lab
DNA methylation profiling to predict recurrence risk in meningioma: development and validation of a nomogram to optimize clinical management
Clinical impact of combined epigenetic and molecular analysis of pediatric low grade gliomas.
The Society for Neuro-Oncology: 20/20 vision for the future.
The central nervous system tumor methylation classifier changes neurooncology practice for challenging brain tumor diagnoses and directly impacts patient care
Integrated models incorporating radiologic and radiomic features predict meningioma grade, local failure, and overall survival.
DNA METHYLATION PROFILING & ANALYSIS REQUEST FORM
Please fill out this form if you are requesting DNA methylation profiling to be completed on your brain tumor sample.