Genetic Alteration Analysis of IDH1, IDH2, CDKN2A, MYB and MYBL1 in Pediatric Low-Grade Gliomas

Orit Barinfeld; Alon Zahavi; Shirel Weiss; Helen Toledano; Shalom Michowiz; Nitza Goldenberg-Cohen

doi:10.3389/fsurg.2022.880048

Genetic Alteration Analysis of IDH1, IDH2, CDKN2A, MYB and MYBL1 in Pediatric Low-Grade Gliomas

Front Surg. 2022 Apr 28:9:880048. doi: 10.3389/fsurg.2022.880048. eCollection 2022.

Authors

Orit Barinfeld^{1

2}, Alon Zahavi^{1

2

3}, Shirel Weiss^{1

2}, Helen Toledano^{1

4}, Shalom Michowiz^{1

5}, Nitza Goldenberg-Cohen^{2

6}

Affiliations

¹ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
² The Krieger Eye Research Laboratory, Bruce and Ruth Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
³ Ophthalmology Department, Rabin Medical Center - Beilinson Hospital, Petach Tikva, Israel.
⁴ Department of Pediatric Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
⁵ Department of Neurosurgery, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
⁶ Department of Ophthalmology, Bnai-Zion Medical Center of Israel, Haifa, Israel.

Abstract

Objective: To investigate pediatric low-grade gliomas for alterations in IDH1, IDH2, CDKN2A, MYB, and MYBL1.

Materials and methods: DNA and RNA were extracted from 62 pediatric gliomas. Molecular methods included PCR, RT-PCR, and RNA sequencing; Sanger sequencing was used for validation.

Results: Analysis for hotspot genetic alterations in IDH1 R132 and IDH2 R172 (45 and 33 samples) was negative in all cases. CDKN2A deletions were detected in exons 1 and 2 in 1 (pleomorphic xanthoastrocytoma) sample of 9 samples analyzed. Of 10 samples analyzed for MYB translocation, 4 each were positive for translocations with exon 2 and exon 3 of PCDHGA1. Six samples showed MYBL rearrangement. The lack of IDH1/2 genetic alterations is in accordance with the literature in pediatric tumors. Alterations in MYB, MYBL were recently reported to characterize diffuse grade II, but not grade I, gliomas.

Conclusion: We optimized methods for analyzing gene variations and correlated the findings to pathological grade. The high incidence of MYB and MYBL need further evaluation. We also compared DNA, RNA, and RNA sequencing results for fusion, translocation, and genetic alterations. More accurate identification of the underlying biology of pediatric gliomas has implications for the development of targeted treatment.

Keywords: CDKN2A; IDH1; MYB; MYBL1; glioma; molecular; pediatric.