Epigenetic Changes Drive this Rare Malignant Paediatric Brain Tumour

A healthy neuron. Credit: NIH

A new study published in Life Science Alliance revealed how aberrant epigenetic regulation contributes to the development of atypical teratoid/rhabdoid (AT/RT) tumours, which mainly affect young children. There is an urgent need for more research in this area as current treatment options are ineffective against these highly malignant tumours.

Most tumours take a long time to develop as harmful mutations gradually accumulate in cells’ DNA over time. AT/RT tumours are a rare exception, because the inactivation of one gene gives rise to this highly aggressive form of brain cancer.

AT/RT tumours are rare central nervous system embryonic tumours that predominantly affect infants and young children.

On average, 73 people are diagnosed with AT/RT in the USA each year. However, AT/RT is the most common central nervous system tumour in children under one years old and accounts for 40-50% of diagnoses in this age group. The prognosis for AT/RT patients is grim, with a postoperative median survival of only 11-24 months.

The collaborative study conducted by Tampere University and Tampere University Hospital examined how aberrant DNA methylation distorts cellular developmental trajectories and thereby contributes to the formation of AT/RT. DNA methylation is a normal process of controlling expression whereby methyl groups are added to the DNA strand, adding epigenetic information.

The new study showed that DNA methylation interferes with the activity of multiple regulators, which usually regulate the differentiation and maturation of central nervous system cells during brain development. Disrupted cell differentiation promotes the abnormal, uncontrolled proliferation of cells that eventually form a tumour.

The study also found several genes that regulate cell differentiation or inhibit tumour development and are silenced in AT/RT together with increased DNA methylation.

“These results will provide deeper insights into the development of AT/RTs and their malignancy. In the future, the results will help to accelerate the discovery of new treatments for this aggressive brain tumour,” says senior author Docent Kirsi Rautajoki from Tampere University.

Source: Tampere University