A new study from The Cancer Genome Atlas Research Network recently revealed the added value of performing genetic analysis in brain tumors. The study is entitled “Comprehensive, Integrative Genomic Analysis of Diffuse Lower-Grade Gliomas” and was published in the New England Journal of Medicine. The study involved more than 300 researchers from 44 different institutions.
Gliomas are a type of cancer that develops in glial cells, which are non-neuronal cells that constitute up to 50% of the brain cells and that provide support and protection for neurons. As the tumor grows, it can compress normal brain tissue, often leading to disability or fatal consequences. It is estimated that 80% of all malignant brain tumors correspond to gliomas, which can be classified by grade according to their histopathological evaluation. The most common grading system from the World Health Organization (WHO) classifies gliomas from I (least advanced disease and a better prognosis) to IV (most advanced disease and a worst prognosis).
Diffuse low-grade (grade II) and intermediate-grade (grade III) gliomas, which together form the lower-grade gliomas, have a highly variable clinical behavior from indolent to highly aggressive that cannot be accurately predicted based on their histological class. In addition, the histologic classification of gliomas can differ between observers. Apart from the histological classification, mutations in the genes IDH, TP53 and ATRX, as well as co-deletion of chromosome arms 1p and 19q (1p/19q), have been reported as clinically relevant biomarkers of lower-grade gliomas.
In the study, researchers conducted genome-wide analyses of 293 lower-grade gliomas from adults in terms of specific genetic features including gene mutations and chromosomal anomalies.
Researchers found that the genetic makeup obtained from the brain tumors analyzed allowed the generation of three robust, non-overlapping and prognostically significant subtypes of lower-grade glioma. Patients with lower-grade gliomas, and an IDH mutation and 1p/19q co-deletion were found to have the most favorable clinical outcomes. The team also found that almost all lower-grade gliomas with IDH mutations and no 1p/19q co-deletion had mutations in the TP53 gene (94%) and ATRX inactivation (86%). The majority of the lower-grade gliomas without IDH mutations exhibited genomic aberrations and a clinical behavior similar to the one observed in aggressive glioblastomas.
“We found molecular signatures that better define clinical behavior based on our analysis,” said the study’s lead co-author Dr. W.K. Alfred Yung from The University of Texas MD Anderson Center in a news release. “We hope this will impact how physicians both diagnose and plan therapies for brain cancer.”
“We looked at the six most common forms of glioma and were able to deduce that these can be effectively grouped into three distinct molecular super clusters of lower-grade gliomas,” explained the study’s lead co-author Dr. Roeland Verhaak also from The University of Texas MD Anderson Center. “It is exciting that our findings are likely to provide a basis for the upcoming update to the WHO classification of tumors of the central nervous system.”
The research team concluded that lower-grade gliomas can be classified into three molecular classes that are more in agreement with IDH, 1p/19q, and TP53 status than with histologic classes. The team believes that their findings might change brain tumor diagnosis, classification and also treatment into a more accurate, consistent and precise manner based on the genetic makeup of the tumor and specific biomarkers. The authors propose that molecular tests combined with the current standard histopathological examination of brain tumors will allow the identification of the tumor aggressiveness and predict its response to certain therapies.