New way to identify brain tumor aggressiveness

New way to identify brain tumor aggressiveness

A comprehensive analysis of the molecular characteristics of gliomas--the most common malignant brain tumor--explains why some patients diagnosed with slow-growing (low-grade) tumors quickly succumb to the disease while others with more aggressive (high-grade) tumors survive for many years. 

Currently, pathologists determine if a glioma is low-grade or high-grade based on the tumor tissue's appearance under the microscope.

"While this approach is generally good at distinguishing between gliomas that are clearly very aggressive and those that are relatively slow-growing, it misses the mark in a significant percentage of cases, leading to inappropriate treatment," said co-senior author.  "Instead, by looking at the molecular makeup of these tumors, we now have a much more precise way of predicting which tumors are more likely to grow rapidly and can prescribe treatments accordingly."

Other researchers have attempted to classify gliomas according to their genetic characteristics. One study found that tumors with mutations in a gene called IDH were significantly less aggressive than those without the mutation, known as IDH wild type tumors. However, these findings did not fully explain why some patients with IDH mutant tumors fare worse than expected and some with IDH wild type tumors fare better than expected. Other studies suggested that a glioma's level of DNA methylation, an epigenetic process that cells use to control gene expression, might explain a tumor's aggressiveness, but the evidence was inconclusive.

In this study, researchers analyzed 1,122 high and low grade glioma samples, looking for epigenetic changes in the tumors' DNA. The researchers found that the best predictor of progression in an IDH mutant glioma--the less-aggressive variety--is its level of DNA methylation. Among IDH mutant gliomas, those with a high degree of DNA methylation progressed more slowly. However, tumors with less DNA methylation, about 6 percent of the total, progressed very quickly.

"Based on their appearance under the microscope, these aggressive tumors looked very much like the other IDH mutant tumors," said the author. "But from a disease prognosis standpoint, they progressed quite similarly to the more lethal subset of IDH wild type gliomas," said the author.

Among those with IDH wild type gliomas--the most aggressive type--a small subset (about 6 percent) had relatively favorable clinical outcomes. The molecular characteristics of this group were similar to those of pilocytic astrocytomas, a childhood brain tumor with a relatively favorable survival rate.

The paper also identified several previously unrecognized genetic alterations that may contribute to glioma development, highlighting potential new targets for drug therapy.