Extrachromosomal DNA: Redefining the pathogenesis of glioblastoma

Glioblastoma is an incurable most prevalent primary malignant brain tumor in adults. Surgery followed by radiotherapy with concomitant chemotherapy is the standard of care in patients with glioblastoma. Although, prognosis remains poor with a median survival in the range of 12-15 months. Over the decades of research has identified the gene mutation, angiogenesis, cell signaling for the development novel therapeutics. However, recent understanding on extrachromosomal DNA (ecDNA) put extra-layer of complexity in glioblastoma pathogenesis. These ecDNAs are present in significantly higher copy number in the nucleus of the cancer cells and contains several oncogenes which are instrumental for intra-tumoral genetic heterogeneity, accelerated tumor evolution and therapy resistance. In this review, we will discuss the current understanding on biogenesis, disease progression and potential therapeutic implications of ecDNAs in glioblastoma.