Abstract PO043: TERT expression increases with tumor grade in a cohort of IDH mutant gliomas

Abstract

Abstract Glioblastoma multiforme is the most deadly primary brain tumor, exhibiting a median survival of just 13 months despite aggressive treatments including surgery, radiation, and chemotherapy. There are two main subtypes of glioblastoma, denoted primary and secondary glioblastoma, respectively. While the former begins as a grade IV tumor, secondary glioblastomas evolve from a lineage that may include grade II astrocytomas and grade III anaplastic astrocytomas, a class of tumors which are molecularly defined by mutations in isocitrate dehydrogenase (IDH). The molecular mechanisms underlying progression of these tumors are poorly understood. Telomerase reverse transcriptase (TERT), a gene encoding for the catalytic subunit of telomerase, is upregulated in a plethora of cancers and represents a probable mechanism by which malignant cells delay senescence and evade cell death. TERT activity is the primary mechanism by which malignant cells replenish telomeres with the other being the alternative lengthening of telomeres (ALT) system, known to become active in tumors harboring loss of function mutations in ATRX. In data obtained from The Cancer Genome Atlas, significantly lower rates of survival were observed in low grade glioma patients with tumors highly expressing TERT as compared to tumors with low/medium expression. However, studies comparing the expression of TERT across different grades of glioma have not been performed to date. Using immunohistochemical staining we show that, controlling for ATRX and IDH mutational status, TERT expression increases as a function of tumor grade in a cohort of patient-derived astrocytoma, anaplastic astrocytoma, and secondary glioblastoma samples. These findings indicate that as astrocytomas progress to more aggressive tumors, TERT expression likely increases to provide enhanced genomic stability. Citation Format: John L. Caniglia, Anvesh Jalasutram, Kiran K. Velpula, Maheedhara R. Guda, Sarah E. Bach, Andrew J. Tsung. TERT expression increases with tumor grade in a cohort of IDH mutant gliomas [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO043.