Central Nervous System Tumour

Central nervous system (CNS) tumour is a disease where abnormal cells form in the tissues of the brain and/or spinal cord. Malignant gliomas are the most common type of primary brain tumours (>70% of all CNS tumours) with different subtypes:
• Astrocytoma
• Oligodendroglioma
• Mixed glioma

Molecular techniques to detect certain generic alterations may influence the survival or therapeutic responsiveness of some CNS neoplasms. Currently, isocitrate dehydrogenase (IDH) mutation, 1p19q co-deletion and MGMT promoter methylation are proven diagnostic biomarkers for CNS tumours[1].

Mutations in isocitrate dehydrogenase (IDH) enzyme isoforms 1 (IDH1) and 2 (IDH2) have been found in 70% of grade II-IV gliomas. IDH mutation testing is very useful as IDH-mutant gliomas are generally associated with good response to treatment and a better prognosis[1-3].

1p19q deletion (combined deletion in short arms 1p and long arm of 19q) is characteristic of oligodendrogliomas. It is important to differentiate astrocytoma from oligodendroglioma as it will affect treatment plan and disease prognosis. 1p19q deletion is specifically useful to predict response to therapy in oligodendrogliomas. The gain of chromosome 19 supports diagnosis of high-grade astrocytoma (glioblastoma multiforme) while the loss of 1p may identify treatment-sensitive high grade oligodendroglioma (for both chemotherapy and radiotherapy)[1-3].

Malignant gliomas may have the O6-methylguanine-DNA methyltransferase (MGMT) gene inactivated due to methylation of its promoter region. Methylation of the MGMT gene promoter is a positive prognostic marker for the response of glioblastoma patients to alkylating chemotherapy (such as temozolomide) and radiotherapy[4].

Oncode offers PCR sequencing assay for the molecular profiling of CNS Tumour.
ONCODEcipher CNS Pinpoint
ONCODEcipher CNS LiquidPinpoint is a PCR-based technique using Multiplex Ligation-dependent Probe Amplification (MLPA) to detect 1p19q deletion, IDH1 & IDH2 mutations.

Specimen Requirements:
• Tumour FFPE block OR 10 FFPE Slides (10µm thick sections) with at least 30% tumour cellularity & 1 H&E stained slide cut from same block AND
• Non-Tumour 3ml blood in EDTA tube OR FFPE Block OR 10 unstained Slides (10µm thick sections) of non-tumour tissue

Turn Around Time:
15 working days

Shipment Requirement:
Keep specimen at room temperature. DO NOT ship on ice or dry ice or expose to direct sunlight.
ONCODEcipher CNS MGMT
ONCODEcipher CNS MGMT is a real time PCR-based technique to detect MGMT methylation.

Specimen Requirements:
• Tumour FFPE block OR 10 FFPE Slides (10µm thick sections) with at least 30% tumour cellularity & 1 H&E stained slide cut from same block AND
• Non-Tumour 3ml blood in EDTA tube OR FFPE Block OR 10 unstained Slides (10µm thick sections) of non-tumour tissue

Turn Around Time:
15 working days

Shipment Requirement:
Keep specimen at room temperature. DO NOT ship on ice or dry ice or expose to direct sunlight.
References:
1. Abel, T., Aldape, K. Clark, S. Vnencak-Jones, C. Mobley, B. (2015). Molecular Profiling of Glioma. My Cancer Genome. READ MORE
2. Frenel, J.S. et al. (2013). Combining Two Biomarkers, IDH1/2 Mutations and 1p/19q Codeletion, to Stratify Anaplastic Oligodendroglioma in Three Groups: A Single-Center Experience. Journal of Neuro-Oncology 114:85–91. doi: 10.1007/s11060-013-1152-0.
3. Zhang, Z.Y., Chan, A.K., Ng, H.K., et al. (2014). Surgically Treated Incidentally Discovered Low-Grade Gliomas are Mostly IDH Mutated and 1p19q Co-Deleted with Favorable Prognosis. International Journal of Clinical and Experimental Pathology 7:8627–8636.
4. Molenaar, R.J., Verbaan, D., Lamba, S., et al. (2014). The combination of IDH1 mutations and MGMT methylation status predicts survival in glioblastoma better than either IDH1 or MGMT alone. Neuro-Oncology 16(9): 1263–1273.