Affiliation:
1. Department of Pathology St. Jude Children's Research Hospital Memphis Tennessee USA
2. Department of Computational Biology St. Jude Children's Research Hospital Memphis Tennessee USA
3. Department of Oncology St. Jude Children's Research Hospital Memphis Tennessee USA
Abstract
AbstractSmall round cell neoplasms comprise a diverse group of tumors characterized by a primitive/undifferentiated appearance. Although several entities are associated with recurrent gene fusions, many of these neoplasms have not been fully characterized, and novel molecular alterations are being discovered. Here, we report an undifferentiated small round cell neoplasm arising in the anterior mediastinum of a 17‐month‐old female. The tumor harbored a novel HNRNPM::LEUTX fusion resulting from chromothripsis of chromosome 19, which was identified by whole transcriptome sequencing, but not by targeted sequencing. The structural variations caused by the chromothripsis event also challenged the interpretation of the targeted sequencing findings. This report expands the spectrum of gene partners involved in LEUTX fusions and underscores the value of whole transcriptome sequencing in the diagnostic workup of undifferentiated small round cell tumors. It also highlights the interpretive challenges associated with complex genomic alterations. A careful evidence‐based analysis of sequencing data along with histopathologic correlation is essential to ensure correct categorization of fusions.