AICT-led team finds IDH-mutant gliomas evolve differently after therapy in 183-patient genomic study

The Advanced Institute of Convergence Technology (AICT), a joint institution of Gyeonggi Province and Seoul National University, reported on 5 November that an international team including Professor Baek Seon-ha and Dr. Moon Hyo-eun analyzed genomic changes in IDH-mutant glioma before and after treatment. According to gg.newdaily.co.kr, the team identified different evolutionary paths for different tumor types gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗. The study was published in Nature on 14 October gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗. It is the institute's second Nature paper since June gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗.

Tumor types and data

IDH-mutant glioma is an adult diffuse glioma with specific mutations in the IDH1 or IDH2 genes. Under the WHO classification, it is divided into astrocytoma and oligodendroglioma by the presence of 1p/19q co-deletion gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗. Both tumors often recur despite surgery, chemotherapy and radiation gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗.

The team used data from the international GLASS consortium. They analyzed whole-genome and whole-exome sequencing of tumors taken before and after treatment from 183 patients with detailed clinical information gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗. The analysis covered gene variants, mutation patterns, chromosomal instability and tumor clonality gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗.

Distinct genomic paths

In astrocytomas, the team observed copy number alterations, such as local amplification of oncogenes, and aneuploidy gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗. In oligodendrogliomas, new mutations that drive tumor progression appeared gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗. An earlier paper from June had shown that genetic changes and the tumor microenvironment act together in glioma progression and recurrence gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗.

The authors consider the results a basis for treatment strategies that account for tumor type and evolution. They also expect the work to serve as a framework for follow-up studies of molecular changes in tumors that have acquired resistance to IDH inhibitors gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗. The paper is titled "Divergent genomic evolution in astrocytomas and oligodendrogliomas" gg.newdaily.co.krgg.newdaily.co.krgg.newdaily.co.krOpen source ↗.