Document Type

Conference Proceeding

Publication Date

6-2024

Publication Title

Journal of Neuropathology and Experimental Neurology

Abstract

Background: Diffuse astrocytoma, MYB- or MYBL1-altered are rare pediatric low-grade gliomas, reported in young adults that are often associated with refractory seizures and generally located in the supratentorial compartment. While GFAP is consistently expressed, interestingly OLIG2 expression (another glial marker) is not a common finding. Here we describe the various associated genetic alterations. Methods: Fourteen cases matching to methylation class (MC), Diffuse astrocytoma, MYB- or MYBL1-altered, were analyzed for structural variants/fusion partners. Results: The median age was 16 years (range 1-64), with male: female ratio of 1:1. All but one was supratentorial (one located in pons). On histology, some showed an angiocentric pattern while others a had distinctive histopathology of a lowgrade diffuse glioma. OLIG2 was negative in 3/6 cases and focally positive in 3/6. RNA analysis detected MYB/MYBL1 alterations in 13/14 cases. Five cases had a productive fusion:

MYB-QKI in 2/5, MYB-EYA4 in 1/5, MYB-PCDHGC3 in 1/ 5, and MYBL1-KHDRBS3 in 1/5. Of the remaining 9 cases, productive fusions involving MYB or MYBL1 was not detected, although gene truncations/non-productive fusions could be found in 8/9 cases. No fusion or mutation was detected in 1 of these 9 cases. Conclusions: MYB- or MYBL1-altered tumors are unusual but have distinctive appearances on histopathology. OLIG2 staining is variable, indicating that this may not be a reliable marker. Genetic alterations involving MYB or MYBL1 are heterogenous including the MYB-QKI fusion which is typically found in angiocentric gliomas. Our case series also found additional fusions including MYB-EYA4, MYB-PCDHGC3 and MYBL1-KHDRBS3. Interestingly, the absence of productive fusions in tumors matching to methylation class MYB/ MYBL1-altered glioma is relatively common, with a high proportion of cases showing MYB/MYBL1 truncation mutations.

Volume

83

Issue

6

First Page

513

Comments

American Association of Neuropathologists 100th Annual Meeting, June 6-9, 2024, Olympic Valley, CA

Last Page

514

DOI

10.1093/jnen/nlae036

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