Lekárska genetika a diagnostika 1/2024

The use of methylation array analyses in the diagnosis of CNS tumors

DNA expression is controlled not only by DNA sequence, but also by epigenetic modifications, which include methylation. DNA methylation mainly occurs in regions of the genome called CpG islands. DNA methylation is able to turn on or turn off gene expression depending on whether the promoter for a given gene is methylated or unmethylated. Tumor cells very often have a deregulated DNA methylation process. The genome of tumor cells is mostly hypomethylated, but specific areas such as the promoters of tumor suppressor genes tend to be hypermethylated, which leads to turning off their expression. In the last decade, a microarray-based method was introduced to analyze the individual methylation profile. Using this method, an online classifier (www.molecularneuropathology.com) was created in the clinical center in Heidelberg, which, together with histopathological and molecular-genetic analysis, can help to make a more accurate diagnosis, personalized treatment and predict response to the treatment. In addition to evaluating the methylation profile, this classifier can also analyze the profile of the copy number variations (amplifications, deletions) of chromosomal regions and entire chromosomes. The general consensus, even considering WHO recommendations, is to investigate methylation in all childhood and diagnostically challenging adult CNS tumors.

Keywords: methylation, DNA, CNS tumors, classifier, copy number variations