Dr. Vijay Ramaswamy, Assistant Professor, Haematology/Oncology, Programme in Neuroscience and Mental Health, Hospital for Sick Children
Project title: “Mechanisms of treatment resistance in supratentorial ependymoma”
Ependymoma is the third most common brain tumour of childhood and can occur anywhere in the brain and spinal cord. A major challenge in neuro-oncology is supratentorial ependymoma which arises in the hemispheres of the brain. Treatment currently consists of surgery and radiation, in children as young as 1 year.
Despite such aggressive therapy, many children still relapse and succumb to their tumour. Moreover survivors are left with lifelong disabilities and are frequently unable to live independent lives due to the effects of radiation on the developing brain. As such, new and novel treatments are urgently required.
This proposal seeks to bridge this gap by understanding why some supratentorial ependymoma’s are resistant to radiation and fail therapy. This will be done by studying the differences in supratentorial ependymoma from both diagnosis and after treatment failure, with the goal of identifying drugs that can be used to target the cause of treatment failure.
These drugs will be combined with radiation to determine if we can make radiation more effective, and even lower its dose. A potential result of this study is to help identify new treatment avenues to improve both survival and quality of life in children with supratentorial ependymoma.
Pairs of recurrent supratentorial ependymoma, and cases of recurrent supratentorial ependymoma have been identified (total of 38 samples), and DNA/RNA extracted using the Qiagen All-Prep DNA/RNA/miRNA kit. Samples have been analysed by Bioanalyzer, and are currently undergoing library preparation for sequencing. So far 8 libraries have been constructed, and 4 libraries have undergone RNA sequencing. The initial analysis of the 4 libraries has shown excellent coverage, and the presence of the canonical RELA fusion. The library preparation was done using the ribodeplete method to ensure that non-PolyA transcripts are also captured. The quality control metrics of these initial samples is excellent, and the additional samples are currently undergoing library prep and sequencing. Immune signatures are currently being deconvoluted from the data, and the analysis will be extended to the entire dataset once the sequencing of all samples is complete.