Longitudinal Molecular Characterization of Oligodendrogliomas

Gordon Y. Ye

Document Type

Article

Publication Date

Summer 2021

JAX Location

In: Student Reports, Summer 2021, The Jackson Laboratory

Abstract

Oligodendrogliomas are a rare subset of diffuse gliomas characterized by mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes and co-deletion of chromosome arms 1p and 19q. Affecting primarily younger patients, oligodendrogliomas offer improved survival compared to other types of gliomas and the treatment course consists of maximal surgical resection followed by treatment with a combined regimen of radiation therapy and temozolomide (an alkylating chemotherapeutic). Previous studies have characterized the longitudinal molecular profiles of diffuse gliomas, including the incidence of a hypermutated phenotype. However, these profiles remain poorly studied in oligodendrogliomas, owing largely to a lack of statistical power. This project leverages matched longitudinal initial and recurrent oligodendroglioma samples from the Glioma Longitudinal AnalySiS Consortium (GLASS) to characterize: 1) the incidence of general and temozolomide-induced hypermutation and their impacts on patient outcomes; and 2) longitudinal changes in mutational profiles as the patients’ tumors recur. We found that temozolomide-induced hypermutation occurs in 40% of oligodendroglioma patients, and that hypermutated tumors recur faster but do not impact overall patient survival. Longitudinal mutation characterization yielded increase doncogenic signaling pathway aberrations and notable increase in CDKN2A deletions from initial to recurrent tumor, as well as mutational signatures unique to hypermutated recurrent oligodendroglioma tumors.

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