Mutation analysis of CDKN2A , MYB, MYBL1 and FGFR1 in pediatric low grade gliomas of the optic pathway

Abstract

Purpose : Gliomas are the commonest type of brain tumors in children. The molecular mechanisms that underlie the development and progression of these tumors are as yet unclear. A better understanding of the molecular mechanisms may improve diagnosis and treatment. In this study we investigate pediatric low grade gliomas for specific mutations in IDH1, IDH2, CDKN2A, MYB, MYBL1 and FGFR1.

Methods : 60 LGG were collected according to institutional and national IRB approval. DNA and RNA were extracted. To detect deletion in CDKN2A and mutations in MYB and MYBL-1, PCR and RT- PCR were performed. RNA seq was performed for 5 grade II and one grade I samples.

Results : CDKN2A deletions in exon 1 and exon 2 were detected in one PXA sample only.
Analysis of the MYB gene revealed 4/9 translocations with exon 2 and 4/9 translocations with exon 3 of the PCDHGA1 gene. Analysis of MYBL -1 showed 6 samples with genetic re-arrangement.

Conclusions : Mutations in MYB, MYBL and FGFR1 genes were recently reported to characterize diffuse grade 2 gliomas but not grade I gliomas. We optimized methods for analyzing gene variations and correlated to pathological grade and prognosis. We compared DNA, RNA and RNA seq results for fusion, translocation and mutations. More accurate identification of the underlying biology of different gliomas and optic pathway gliomas may pave the way for personalized medicine. This will enable targeted treatment and more accurate classification.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.