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Brain cancer treatment modifies tumor DNA behavior

Study published in the journal Cancer Research reveals that treatments commonly used to combat glioma – one of the most common types of brain cancer – can alter the way tumor DNA behaves and its aggressiveness. According to the authors, the discovery may represent a first step towards modifications in the current therapeutic approach.

Gliomas represent around 42% of all brain tumors, including benign ones, and 77% of malignant ones, that is, those that are aggressive and incurable, according to data from the ACCamargo Cancer Center. The incidence of the disease, which is rare in children, increases with age, being more common in people between 75 and 84 years old.

One of the most relevant characteristics for classifying the aggressiveness and severity of this type of tumor in patients are the so-called epigenomic changes, that is, biochemical processes that modify the expression pattern of genes, such as DNA methylation (addition of a methyl group to the molecule). This fact was previously verified, in 2016, by the same group of researchers from the Ribeirão Preto Faculty of Pharmaceutical Sciences of the University of São Paulo (FCFRP-USP) who signed the new article.

The research was conducted at the Cancer Epigenomics Laboratory at FCFRP-USP (photo: researchers’ collection)

“We observed in patients with low-grade tumors who received treatment an epigenetic change that left these tumors similar to high-grade tumors, which are much more aggressive; Therefore, there appears to be an association between the treatment and changes in the DNA of these patients”, explains Tathiane Malta, first author of the study and coordinator of the Cancer Epigenomics Laboratory at FCFRP-USP. “Now, we need to confirm whether these epigenetic changes are involved in the progression to more aggressive tumors.”

In the current study, carried out within the scope of a Young Researcher Research Assistance from FAPESP, scientists evaluated the epigenetic evolution of gliomas in response to therapeutic pressure, analyzing the results of samples from 132 patients. The data included information on both the primary tumor and the one that recurred after treatment, which allowed for better comparison. This is the largest group of longitudinal gliomas ever recorded in the scientific literature.

Several aspects related to changes in the epigenome could be observed, such as greater proliferation of tumor cells, an increase in vascular cells in the tumor and changes in the tumor microenvironment. However, one stood out: IDH1 mutant patients (with a better initial prognosis) who were treated with chemotherapy or radiotherapy showed greater changes in the tumor epigenome.

“We saw that these gliomas present high initial levels of DNA methylation, which are progressively reduced when the disease recurs after chemotherapy or radiotherapy, and become more aggressive”, says Malta. “The epigenome of IDH wild-type patients – the initially more aggressive ones – is more stable, with relatively low levels of methylation, that is, in this case, the primary tumors are very similar to the recurrent ones, including because they were already at a maximum level. aggressive.”

“This means that the treatment, in some way, modifies this tumor, and this change is associated with aggressiveness.”

Changes in therapeutic approach

According to Malta, by demonstrating that epigenetic regulation is associated with cancer progression, the work contributes to a better understanding of tumor biology and, consequently, opens up space for new therapeutic approaches with this direction.

The next steps to understand the implications of the discovery and evaluate its real impact on the treatment of gliomas must initially include carrying out treatments in vitro in tumor lines and, subsequently, in models in vivo to confirm the results already obtained.

“As in this study we are based on a retrospective cohort, with data collected from many institutions and clinical management that have undergone changes over time, it is necessary to consider the presence of several biases.”

The article The epigenetic evolution of glioma is determined by the IDH1 mutation status and treatment regimen can be read at: https://aacrjournals.org/cancerres/article/84/5/741/734933/The-Epigenetic-Evolution-of-Glioma-Is-Determined .

Source: CNN Brasil

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