DNA methylation-based profiling for paediatric CNS tumour diagnosis and treatment: a population-based study

Invited Review: DNA methylation‐based classification of paediatric brain tumours

“…For this the probe intensities are used to calculate low‐density copy number variation plots . Even though they are clearly less dense than other arrays used for brain tumour classification and there may be a danger of missing subclonal events , the data offers broad diagnostic applications recently reviewed elsewhere . Guidance for additional molecular testing : The fourth level of information is slightly more abstract and is derived from the mostly unexplained but very tight association of DNA methylation classes with certain mutation events or specific gene fusions. This tight association has substantial potential to guide additional molecular testing, in particular in the rapidly expanding field of gene fusions.…”

“…MYCN , MYC , GLI2 ), isochromosome 17q, deletion of chromosome 6 and whole‐chromosomal aberration signatures may be the most relevant . It must be taken into consideration that as with every tumour bulk analysis, subclonal events (such as some amplifications) may be missed . DNA methylation profiling further offers certain guidance for additional molecular testing.…”

“…An important role of methylation profiling lies in the classification of low‐grade gliomas that present with unusual or malignant histological features (see also paragraph on Paediatric gliomas with malignant histological features above). It has been observed that methylation profiling may be less straight forward for tumours from the spectrum of low‐grade gliomas , possibly owing to the frequently low tumour cell content or the missing representation of several methylation classes in commonly used classifiers . Tumour sub‐classification has been established for pilocytic astrocytoma where three different location‐dependent subclasses are defined .…”

“…At present, DNA methylation profiling offers relevant diagnostic information for the vast majority of paediatric brain tumours. A rational implementation of DNA methylation profiling into pathological routine, especially for cases with ambiguous histology or non‐informative or contradictory molecular information will improve diagnostic precision and will have a substantial impact on patient management . For the currently rapidly expanding number of brain tumour classes and sub‐classes it may represent a unifying diagnostic tool that can be applied across many types of cancer and will frequently give sound diagnostic suggestions and guidance for additional molecular testing.…”

Research in practice: fitting it together

“…In other cases, genes, signatures and proteins identified by high throughput technologies have led to the generation of specific cheap tests, such as immunohistochemical stains, to quickly evaluate for certain markers of disease and in areas such as paediatric brain tumours, advanced molecular profiling has revolutionised both the classification and diagnosis of some tumour types. 9 However, it is not just molecular testing, advances in imaging, such as MR spectroscopy, 10 enable us to understand more and get greater precision with noninvasive tests. Neonatal MRI is giving us new information and becoming more widespread, though how best to use this in the 'real world' remains a challenge.…”