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Oligodendroglioma Subgroups Identified Using Multiple Omics Profiling

NEW YORK (GenomeWeb) – A known subtype of oligodendroglioma can be further sub-classified molecularly, according to a study published online this week in Nature Communications.

Through the "Prise en charge des oligodendrogliomes anaplasiques," (POLA) study, French researchers brought together genome, transcriptome, and methylome profiles for tumors from 156 individuals with oligodendroglia. Their analyses not only supported the presence of three known molecular sub-types, but also made it possible to subdivide one of these — a subtype defined by co-deletions involving parts of chromosome 1 and chromosome 19 — into three additional sub-groups.

"The clinical significance of the three gene expression sub-groups of 1p/19q co-deleted tumors remains to be determined since association with survival was only observed in the [Cancer Genome Atlas] dataset and not in the three other cohorts," the study's authors wrote, noting that it will be important to more carefully tease apart survival outcomes in order to come up with appropriate classification and treatment strategies for the newly described subgroups.

Past low-grade glioma studies suggest oligodendrogliomas fall into three main molecular subtypes, marked by the presence or absence of IDH gene mutations or by co-deletions involving parts of chromosomes 1 and 19. Even so, the team suspected that it might be possible to further stratify the tumors, which tend to be clinically, molecularly, and histologically variable.

For the latest analysis, the researchers used a combination of genomic approaches to profile 156 primary oligodendroglial tumors, 14 other primary glioma tumors, and nine normal samples.

In addition to doing transcriptome sequencing on all of these, they sequenced microRNAs in all but two of the samples. To that, they added array-based SNP and methylation profiling on 161 and 104 samples, respectively.

After removing a subset of 29 tumors that clustered with normal brain samples, the team looked at the ways the remaining samples grouped together based on each type of data alone and in combination.

The analysis uncovered molecular profiles that fit with the three known oligodendroglioma subtypes. But within the chromosome 1-chromosome 19 co-deletion tumors, the team described three sub-groups with gene expression patterns that resemble those in oligodendrocyte cells, oligodendrocyte precursor cells, or cells from the neuronal lineage.

While chromosome 1/19 co-deletion tumors are typically associated with better outcomes than the other two oligodendroglioma subtypes, the researchers saw hints that the oligodendrocyte precursor cell-like expression subgroup had enhanced aggressiveness, at least in available data from the Cancer Genome Atlas project.

That appears to be due, in part, to activation of the MYC signaling pathway caused by gains, losses, or changes in the pathway's methylation or miRNA regulators. The aggressive subgroup also tended to have higher-than-usual expression of genes involved in cell cycle control, new blood vessel formation, and tumor progression.

In both the POLA and TCGA data, chromosome 1/19 co-deletion tumors with oligodendrocyte precursor cell-like expression features tended to turn up more frequently in patients who were slightly older at diagnosis, the study's authors noted. 

"Our study reveals previously unrecognized heterogeneity among 1p/19q co-deleted tumors," they wrote.