Optical Genome Mapping Identifies a Novel Pediatric Embryonal Tumor Subtype with a ZNF532-NUTM1 Fusion

Abstract

Molecular characteristics of pediatric brain tumors have not only allowed for tumor subgrouping but have introduced novel treatment options for patients with specific tumor alterations. Therefore, an accurate histologic and molecular diagnosis is critical for optimized management of all pediatric patients with brain tumors, including central nervous system embryonal tumors. We present a case where optical genome mapping identified a ZNF532-NUTM1 fusion in a patient with a unique tumor best characterized histologically as a central nervous system embryonal tumor with rhabdoid features. Additional analyses including immunohistochemistry for NUT protein, methylation array, whole genome, and RNA-sequencing was done to confirm the presence of the fusion in the tumor. This is the first description of a pediatric patient with a ZNF532-NUTM1 fusion, yet the histology of this tumor is similar to that of adult cancers with ZNF-NUTM1 fusions and other NUTM1-fusion positive brain tumors reported in literature. Although rare, the distinct pathology and underlying molecular characteristics of these tumors separate them from other embryonal tumors. Therefore, the NUTM-rearrangement appears to define a novel subgroup of pediatric central nervous system embryonal tumors with rhabdoid/epithelioid features that may have a unique response to treatment. Screening for a NUTM1-rearrangement should be considered for all patients with unclassified central nervous system tumors with rhabdoid features to ensure accurate diagnosis so this can ultimately inform therapeutic management for these patients.