Astroblastoma With a Novel YAP1::BEND2 Fusion: A Case Report

Area of Science:

• Neuro-oncology
• Molecular Pathology
• Genetics of Brain Tumors

Background:

• The 5th edition WHO Classification of CNS Tumors defines astroblastoma by MN1 gene rearrangements (astroblastoma, MN1-altered).
• Recent studies identified EWSR1::BEND2 fusion gliomas with astroblastoma-like features, distinct epigenetically but lacking MN1 alterations.
• These EWSR1::BEND2 fusion tumors do not meet current molecular criteria for astroblastoma despite histomorphologic similarities.

Purpose of the Study:

• To report a case of astroblastoma-like glioma with a novel YAP1::BEND2 fusion.
• To investigate molecular findings in astroblastoma-like tumors beyond MN1 alterations.
• To challenge the current molecular classification of astroblastoma.

Main Methods:

• Histologic examination of a glioma case.
• DNA methylation profiling.
• Identification of gene fusions (YAP1::BEND2).

Main Results:

• A case of glioma with histomorphologic and DNA methylation features consistent with astroblastoma was identified.
• This case harbored a novel YAP1::BEND2 gene fusion.
• This finding, along with prior EWSR1::BEND2 fusion cases, demonstrates astroblastoma-like tumors with molecular alterations independent of MN1.

Conclusions:

• The molecular landscape of astroblastoma-like tumors is broader than currently defined by MN1 alterations.
• Novel gene fusions, such as YAP1::BEND2, expand the spectrum of molecular findings in these challenging CNS tumors.
• Current classification criteria for astroblastoma require re-evaluation to encompass these newly identified molecular subtypes.