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

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.

Benchmarking long-read genome sequence alignment tools for human genomics applications

“…Optical genome mapping (developed by Bionano Genomics, San Diego, CA, USA) excels at detecting structural variants (SV), such as balanced translocations and deletions/insertions in the 1 kb to 1 Mb range, and its clinical utility was demonstrated in Duchenne (DMD) or facioscapulohumeral (FSHD) muscular dystrophies ( Barseghyan et al, 2017 ; Sharim et al, 2019 ), and cancer ( Neveling et al, 2021 ; Talsania et al., 2022 ; Bornhorst et al, 2023 ). But long-read sequence (LRS), developed by Pacific Biosciences (Menlo Park, CA, USA) and Oxford Nanopore Technologies (Oxford, UK) among others, has been shown to be the most appropriate technology to detect smaller variants in the 50 bp-1 kb range ( Chaisson et al, 2019 ).…”