Persistent STAG2 mutation despite multimodal therapy in recurrent pediatric glioblastoma.

NPJ Genomic Medicine
Christopher S HongE Zeynep Erson-Omay

Abstract

Similar to their adult counterparts, the prognosis for pediatric patients with high-grade gliomas remains poor. At time of recurrence, treatment options are limited and remain without consensus. This report describes the genetic findings, obtained from whole-exome sequencing of a pediatric patient with glioblastoma who underwent multiple surgical resections and treatment with standard chemoradiation, as well as a novel recombinant poliovirus vaccine therapy. Strikingly, despite the variety of treatments, there was persistence of a tumor clone, characterized by a deleterious STAG2 mutation, whose deficiency in preclinical studies can cause aneuploidy and aberrant mitotic progression, but remains understudied in the clinical setting. There was near elimination of an EGFR mutated and amplified tumor clone after gross total resection, standard chemoradiation, and poliovirus therapy, followed by the emergence of a persistently STAG2 mutated clone, with rare mutations in PTPN11 and BRAF, the latter composed of a novel deleterious mutation previously not reported in pediatric glioblastoma (p.D594G). This was accompanied by a mutation signature shift towards one characterized by increased DNA damage repair defects, consistent with the ...Continue Reading

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Methods Mentioned

BETA
surgical resection
exome sequencing

Clinical Trials Mentioned

NCT02986178

Software Mentioned

fishplot R package
ClonEvol
Genome Analysis Toolkit ( GATK
MutationalPatterns R package
fishplot

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