Event Title

Inhibiting Epigenetic Histone Methylation Within Pediatric Brainstem Glioma via PRC2 Methyltransferase

Session Number

Q30

Advisor(s)

Rintaro Hashizume, Northwestern University
Quanhong Grace Ma, Northwestern University

Location

B-116

Start Date

28-4-2016 1:35 PM

End Date

28-4-2016 2:00 PM

Disciplines

Neuroscience and Neurobiology

Abstract

The pediatric brainstem glioma is one of the most deadly malignancies throughout the human body. Such pediatric central nervous system tumors are found to compose of approximately ten percent of all central nervous system malignancies in children. Thus, in attempts to inhibit this neoplastic growth, it was found that a protein complex associated with an epigenetic factor known as PRC2 methyltransferase was inhibited by the histone H3F3A gene mutation (K27M) in the encoded histone H3.3 protein that occurred in sixty percent of brainstem gliomas. This reduced methylation-induced gene silencing: creating abhorrent growth. As such, to counteract this neoplastic mutation, tests were performed to determine what aspect of the PRC2 methyltransferase complex could be modified to overcome the K27M mutation. Through analysis of the protein complex, SUZ12, a component of the PRC2 complex, was determined to be a potential target. After which, genomic editing of the glioma DNA was performed to remove SUZ12. This modified cellular DNA was then transfected and expressed in vitro cultures to observe the actual impact of SUZ12 absence in relation to tumor growth. This, in turn, exhibited the protein’s significant impact upon uncontrolled growth and its inhibition was found to be a valuable anti-cancer target.


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Apr 28th, 1:35 PM Apr 28th, 2:00 PM

Inhibiting Epigenetic Histone Methylation Within Pediatric Brainstem Glioma via PRC2 Methyltransferase

B-116

The pediatric brainstem glioma is one of the most deadly malignancies throughout the human body. Such pediatric central nervous system tumors are found to compose of approximately ten percent of all central nervous system malignancies in children. Thus, in attempts to inhibit this neoplastic growth, it was found that a protein complex associated with an epigenetic factor known as PRC2 methyltransferase was inhibited by the histone H3F3A gene mutation (K27M) in the encoded histone H3.3 protein that occurred in sixty percent of brainstem gliomas. This reduced methylation-induced gene silencing: creating abhorrent growth. As such, to counteract this neoplastic mutation, tests were performed to determine what aspect of the PRC2 methyltransferase complex could be modified to overcome the K27M mutation. Through analysis of the protein complex, SUZ12, a component of the PRC2 complex, was determined to be a potential target. After which, genomic editing of the glioma DNA was performed to remove SUZ12. This modified cellular DNA was then transfected and expressed in vitro cultures to observe the actual impact of SUZ12 absence in relation to tumor growth. This, in turn, exhibited the protein’s significant impact upon uncontrolled growth and its inhibition was found to be a valuable anti-cancer target.