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Molecular characteristics of incidental lower-grade glioma for treatment decision-making

Jeongman Park, Jeongmin Sim, Juwon Ahn, Yu Jin Kim, Sojung Hwang, Kyunggi Cho, Da-Young Chang, Jin-Hwa Jung, Ju Hyung Moon, KyoungSu Sung, and Jaejoon Lim

OBJECTIVE

Several limitations are associated with the early diagnosis and treatment of incidental lower-grade glioma (iLGG), and due to its unknown molecular features, its management is categorized as either the “wait-and-see” strategy or immediate treatment. Therefore, in this study the authors explored iLGG’s clinical and molecular landscape to improve its management.

METHODS

The authors retrospectively assessed the differences between the molecular and clinical characteristics of iLGG and symptomatic lower-grade glioma (sLGG) samples filtered based on symptom data corresponding to The Cancer Genome Atlas cohort with mutations. Thereafter, genomic and transcriptomic analysis was performed.

RESULTS

There was no significant difference between iLGG and sLGG with respect to mutation status; however, there was an increase in the interaction between major mutations in sLGG, depending on the histological subtype and the IDH1 mutation status. Furthermore, the IDH1 mutation characteristics corresponding to wild-type glioma were much more obvious in sLGG than in iLGG. Additionally, in sLGG, genes associated with malignancy, including cell proliferation–related, cell migration–related, epithelial-to-mesenchymal transition–related, and negative regulation of cell death–related genes, were significantly upregulated, and groups showing higher expression levels of these genes were associated with worse prognosis. Also, 8 of the 75 identified upregulated genes showed positive correlation with resistance to the drugs that are normally used for glioma treatment, including procarbazine, carmustine, vincristine, and temozolomide.

CONCLUSIONS

The new insights regarding the different molecular features of iLGG and sLGG indicated that the immediate management of iLGG could result in better prognosis than the wait-and-see strategy.