Each year in Australia approximately 618 children are diagnosed with cancer. Although paediatric cancer is rare, it is the second most common cause of childhood death in Australia, accounting for 17% of deaths each year. The most prevalent paediatric cancers are leukaemia and cancer of the central nervous system (CNS), accounting for one third and one fifth of diagnoses respectively. Despite its lower prevalence, CNS cancer is responsible for more paediatric deaths than leukaemia. The ten year survival rate for CNS cancer is 67.7% and has improved little over the past fifteen years. Additionally, the severity of treatment leaves 90% of survivors with at least one chronic medical condition. Given the poor prognosis and damaging long term effects, furthering our understanding of CNS cancer is essential.
DNA methylation aberrations are a universal feature of cancer. In comparison to the healthy cell, malignant neoplastic cells typically exhibit a pattern of genome wide hypomethylation and promoter specific hypermethylation. DNA methylation research in adult cancer has furthered understanding of the development of these cancers, and identified biomarkers for diagnosis and prognosis. Given the limited understanding and poor prognosis of paediatric CNS cancers it is logical to extend such research into this disease.
We profiled genome-wide methylation changes in paediatric CNS tumours using the HM450 array then validated and extended the findings with a locus-specific analysis platform. The HM450 array analysis demonstrated a difference in methylation between tumour and non-tumour tissue, between tumour sub-types, and between good and poor outcome cases. Locus-specific analysis was then used to identify (i) potential biomarkers for diagnosis and/or prognosis and (ii) disrupted pathways involved in development of these tumours. This analysis demonstrated that the gene promoter regions of RASSF1, PTCH1, and SPRED3 are unsuitable as biomarkers for diagnosis or prognosis in paediatric CNS tumours. However, it did identify a potential role for the PTCH1 gene in the development of paediatric medulloblastoma and CPP tumours.