A recurrent novel MGA-NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma

-rearranged tumors are defined by the presence of a gene fusion between and various gene partners and typically follow a clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. -rearranged tumors display histologic features of a poorly differentiated carci...

Full description

Saved in:
Bibliographic Details
Published in:Cold Spring Harbor molecular case studies 2018-12, Vol.4 (6), p.a003194
Main Authors: Diolaiti, Daniel, Dela Cruz, Filemon S, Gundem, Gunes, Bouvier, Nancy, Boulad, Mathieu, Zhang, Yanming, Chou, Alexander J, Dunkel, Ira J, Sanghvi, Rashesh, Shah, Minita, Geiger, Heather, Rahman, Sadia, Felice, Vanessa, Wrzeszczynski, Kazimierz O, Darnell, Robert B, Antonescu, Cristina R, French, Christopher A, Papaemmanuil, Elli, Kung, Andrew L, Shukla, Neerav
Format: Article
Language:English
Subjects:
Amino acid sequence
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Biomarkers, Tumor - genetics
Cell Differentiation - genetics
Child
Diagnostic systems
Differentiation
Disease control
Exons
Female
Fluorescence
Fluorescence in situ hybridization
Fusion protein
Gene expression
Gene Fusion - genetics
Gene Rearrangement
Gene sequencing
Genomes
Humans
Immunohistochemistry
Male
Mesenchyme
Mutation
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Oncogene Proteins, Fusion - genetics
Proteins
Radiation
Radiation measurement
Recombination, Genetic - genetics
Research Report
Sarcoma
Sarcoma - genetics
Sarcoma - metabolism
Sarcoma, Synovial - genetics
Surgery
Transcription Factors - genetics
Translocation, Genetic - genetics
Tumors
Whole Genome Sequencing - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:-rearranged tumors are defined by the presence of a gene fusion between and various gene partners and typically follow a clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. -rearranged tumors display histologic features of a poorly differentiated carcinoma with areas of focal squamous differentiation and typically express the fusion gene defining a distinct clinicopathologic entity-NUT carcinoma (NC). NCs with mesenchymal differentiation have rarely been described in the literature. In this report, we describe the characterization of two cases of high-grade spindle cell sarcoma harboring a novel fusion. Whole-genome sequencing identified the presence of complex rearrangements resulting in a fusion gene in the absence of other significant somatic mutations. Genetic rearrangement was confirmed by fluorescence in situ hybridization, and expression of the fusion gene product was confirmed by transcriptomic analysis. The fusion protein was predicted to retain nearly the entire protein sequence of both MGA (exons 1-22) and NUTM1 (exons 3-8). Histopathologically, both cases were high-grade spindle cell sarcomas without specific differentiation markers. In contrast to typical cases of NC, these cases were successfully treated with aggressive local control measures (surgery and radiation) and both patients remain alive without disease. These cases describe a new subtype of -rearranged tumors warranting expansion of diagnostic testing to evaluate for the presence of or alternative gene fusions in the diagnostic workup of high-grade spindle cell sarcomas or small round blue cell tumors of ambiguous lineage.
ISSN:2373-2865
2373-2873
DOI:10.1101/mcs.a003194