Optical genome mapping identifies a novel pediatric embryonal tumor with a ZNF532::NUTM1 fusion

Miriam Bornhorst, Division of Hematology/Oncology, Children's National Hospital, Washington, DC, USA.
Augustine Eze, Brain Tumor Institute, Children's National Hospital, Washington, DC, USA.
Surajit Bhattacharya, Center for Genetics Medicine Research, Children's National Hospital, Washington, DC, USA.
Ethan Putnam, Brain Tumor Institute, Children's National Hospital, Washington, DC, USA.
M Isabel Almira-Suarez, Divison of Pathology, Children's National Hospital, Washington, DC, USA.
Christopher Rossi, Divison of Pathology, Children's National Hospital, Washington, DC, USA.
Madhuri Kambhampati, Center for Genetics Medicine Research, Children's National Hospital, Washington, DC, USA.
Miguel Almalvez, Center for Genetics Medicine Research, Children's National Hospital, Washington, DC, USA.
Mariam Barseghyan, Department of Obstetrics and Gynecology, MedStar Georgetown University Hospital, Washington, DC, USA.
Nicole Del Risco, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.
David Dotson, College of Wooster, Wooster, OH, USA.
Joyce Turner, Division of Genetics and Metabolism, Children's National Hospital, Washington, DC, USA.
John S. Myseros, Division of Neurosurgery, Children's National Hospital, Washington, DC, USA.
Eric Vilain, Center for Genetics Medicine Research, Children's National Hospital, Washington, DC, USA.
Roger J. Packer, Brain Tumor Institute, Children's National Hospital, Washington, DC, USA.
Javad Nazarian, Brain Tumor Institute, Children's National Hospital, Washington, DC, USA.
Brian Rood, Division of Hematology/Oncology, Children's National Hospital, Washington, DC, USA.
Hayk Barseghyan, Center for Genetics Medicine Research, Children's National Hospital, Washington, DC, USA.

Document Type

Journal Article

Publication Date

7-1-2023

Journal

The Journal of pathology

Volume

260

Issue

3

DOI

10.1002/path.6085

Keywords

ZNF532::NUTM1; brain tumor; embryonal; optical genome mapping; pediatric

Abstract

The molecular characteristics of pediatric brain tumors have not only allowed for tumor subgrouping but have led to the introduction of 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 reported in the literature. Although rare, the distinct pathology and underlying molecular characteristics of the ZNF532::NUTM1 tumor separates this from other embryonal tumors. Therefore, screening for this or similar NUTM1 rearrangements should be considered for all patients with unclassified central nervous system tumors with rhabdoid features to ensure accurate diagnosis. Ultimately, with additional cases, we may be able to better inform therapeutic management for these patients. © 2023 The Pathological Society of Great Britain and Ireland.

Department

Pediatrics

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