Rise of oligodendroglioma hypermutator phenotype from a subclone harboring TP53 mutation after TMZ treatment

We report a case of 51-year-old woman with a left fronto-temporal oligodendroglioma that contained a small portion with aTP53 mutation, R248Q, at the initial surgery. On a first, slow-growing recurrence 29  months after radiation and nitrosourea-based chemotherapy, the patient underwent TMZ chemotherapy. The recurrent tumor responded well to TMZ but developed a rapid progression after 6 cycles as a malignant hypermutator tumor with aMSH6 mutation. Most of the recurrent tumor lacked typical oligodendroglioma morphology that was observed in the primary tumor, while it retained theIDH1 mutation and 1p/19q co-deletion. The identicalTP53 mutation observed in the small portion of the primary tumor was universal in the recurrence. This case embodied the theoretically understandable clonal expansion of theTP53 mutation with additional mismatch repair gene dysfunction leading to hypermutator phenotype. It thus indicated thatTP53 mutation in oligodendroglioma, although not common, may play a critical role in the development of hypermutator after TMZ treatment.
Source: Brain Tumor Pathology - Category: Neurology Source Type: research