A study conducted by researchers from the D'Or Institute for Research and Education (IDOR) and the Rede D'Or Pathological Anatomy in conjunction with several North American institutions, including the National Cancer Institute (NIH), used new molecular analyses to unravel the biological mechanisms of paediatric brain tumours and refine their classification.

The research results were recently published in the journal Acta Neuropathologica Communications.

Embryonal tumours of the central nervous system (CNS) are a class of malignant tumours composed of embryonal neuroepithelial cells predominantly found in children. Recent updates by the World Health Organization (WHO) classification included several new subtypes of these tumours, highlighting the increasing importance of epigenetic studies in defining these subcategories.

Epigenetic studies, particularly DNA methylation profiling, have an increasing importance in the classification of brain tumours and new tumour types delineation.

The technique application allowed the identification of a particular group of cases where genetic analysis revealed a specific molecular alteration (fusion involving the BRD4 and LEUTX genes).

The BRD4 gene (Bromodomain Containing 4) acts in transcriptional regulation and development, as well as maintaining the pluripotency of stem cells, and its dysregulation has been associated with different types of cancer, as it contributes to cell proliferation and tumour progression. On the other hand, the LEUTX gene (Leucine Twenty Homeobox) plays a role in embryonic development and regulation of early cell differentiation.

In this study, careful analysis of four new cases with these molecular alterations and five other cases described individually in the literature revealed similar clinical, radiological, and histopathological characteristics, indicating that they are most likely a specific type of tumour.

All patients were children up to 4 years old, with bulky tumours, rapid growth, and aggressive clinical behaviour. However, some cases responded well to chemotherapy.

Although the sample size is small, preliminary results indicated that these tumours are clinically aggressive, requiring personalised treatment strategies that combine chemotherapy with total surgical removal of the tumour. It is worth noting that small molecule BRD4 inhibitors and BRD4 degraders have shown promising results in preliminary studies in haematological and solid malignancies and may represent a future therapeutic avenue for these aggressive CNS tumours.

Source: D'Or Institute for Research and Education