Cargando…
A recurrent novel MGA–NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma
NUTM1-rearranged tumors are defined by the presence of a gene fusion between NUTM1 and various gene partners and typically follow a clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. NUTM1-rearranged tumors display histologic features of a poorly diff...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318763/ https://www.ncbi.nlm.nih.gov/pubmed/30552129 http://dx.doi.org/10.1101/mcs.a003194 |
_version_ | 1783384943919890432 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Diolaiti, Daniel |
collection | PubMed |
description | NUTM1-rearranged tumors are defined by the presence of a gene fusion between NUTM1 and various gene partners and typically follow a clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. NUTM1-rearranged tumors display histologic features of a poorly differentiated carcinoma with areas of focal squamous differentiation and typically express the BRD4–NUTM1 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 MGA–NUTM1 fusion. Whole-genome sequencing identified the presence of complex rearrangements resulting in a MGA–NUTM1 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 NUTM1-rearranged tumors warranting expansion of diagnostic testing to evaluate for the presence of MGA–NUTM1 or alternative NUTM1 gene fusions in the diagnostic workup of high-grade spindle cell sarcomas or small round blue cell tumors of ambiguous lineage. |
format | Online Article Text |
id | pubmed-6318763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63187632019-01-13 A recurrent novel MGA–NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma 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 Cold Spring Harb Mol Case Stud Research Report NUTM1-rearranged tumors are defined by the presence of a gene fusion between NUTM1 and various gene partners and typically follow a clinically aggressive disease course with poor outcomes despite conventional multimodality therapy. NUTM1-rearranged tumors display histologic features of a poorly differentiated carcinoma with areas of focal squamous differentiation and typically express the BRD4–NUTM1 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 MGA–NUTM1 fusion. Whole-genome sequencing identified the presence of complex rearrangements resulting in a MGA–NUTM1 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 NUTM1-rearranged tumors warranting expansion of diagnostic testing to evaluate for the presence of MGA–NUTM1 or alternative NUTM1 gene fusions in the diagnostic workup of high-grade spindle cell sarcomas or small round blue cell tumors of ambiguous lineage. Cold Spring Harbor Laboratory Press 2018-12 /pmc/articles/PMC6318763/ /pubmed/30552129 http://dx.doi.org/10.1101/mcs.a003194 Text en © 2018 Diolaiti et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
spellingShingle | Research Report 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 A recurrent novel MGA–NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma |
title | A recurrent novel MGA–NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma |
title_full | A recurrent novel MGA–NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma |
title_fullStr | A recurrent novel MGA–NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma |
title_full_unstemmed | A recurrent novel MGA–NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma |
title_short | A recurrent novel MGA–NUTM1 fusion identifies a new subtype of high-grade spindle cell sarcoma |
title_sort | recurrent novel mga–nutm1 fusion identifies a new subtype of high-grade spindle cell sarcoma |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318763/ https://www.ncbi.nlm.nih.gov/pubmed/30552129 http://dx.doi.org/10.1101/mcs.a003194 |
work_keys_str_mv | AT diolaitidaniel arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT delacruzfilemons arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT gundemgunes arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT bouviernancy arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT bouladmathieu arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT zhangyanming arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT choualexanderj arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT dunkeliraj arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT sanghvirashesh arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT shahminita arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT geigerheather arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT rahmansadia arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT felicevanessa arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT wrzeszczynskikazimierzo arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT darnellrobertb arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT antonescucristinar arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT frenchchristophera arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT papaemmanuilelli arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT kungandrewl arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT shuklaneerav arecurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT diolaitidaniel recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT delacruzfilemons recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT gundemgunes recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT bouviernancy recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT bouladmathieu recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT zhangyanming recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT choualexanderj recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT dunkeliraj recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT sanghvirashesh recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT shahminita recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT geigerheather recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT rahmansadia recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT felicevanessa recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT wrzeszczynskikazimierzo recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT darnellrobertb recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT antonescucristinar recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT frenchchristophera recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT papaemmanuilelli recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT kungandrewl recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma AT shuklaneerav recurrentnovelmganutm1fusionidentifiesanewsubtypeofhighgradespindlecellsarcoma |