NUTM1 gene fusions characterize a subset of undifferentiated soft tissue and visceral tumors Journal Article
| Authors: | Dickson, B. C.; Sung, Y. S.; Rosenblum, M. K.; Reuter, V. E.; Harb, M.; Wunder, J. S.; Swanson, D.; Antonescu, C. R. |
| Article Title: | NUTM1 gene fusions characterize a subset of undifferentiated soft tissue and visceral tumors |
| Abstract: | NUT midline carcinoma is an aggressive tumor that occurs mainly in the head and neck and, less frequently, the mediastinum and lung. Following identification of an index case of a NUTM1 fusion positive undifferentiated soft tissue tumor, we interrogated additional cases of primary undifferentiated soft tissue and visceral tumors for NUTM1 abnormalities. Targeted next-generation sequencing was performed on RNA extracted from formalin-fixed paraffin-embedded tissue, and results validated by fluorescence in situ hybridization using custom bacterial artificial chromosome probes. Six patients were identified: mean age of 42 years (range, 3 to 71 y); equal sex distribution; and, tumors involved the extremity soft tissues (N=2), kidney (N=2), stomach, and brain. On systemic work-up at presentation all patients lacked a distant primary tumor. Morphologically, the tumors were heterogenous, with undifferentiated round-epithelioid-rhabdoid cells arranged in solid sheets, nests, and cords. Mitotic activity was generally brisk. Four cases expressed pancytokeratin, but in only 2 cases was this diffuse. Next-generation sequencing demonstrated the following fusions: BRD4-NUTM1 (3 cases), BRD3-NUTM1, MXD1-NUTM1, and BCORL1-NUTM1. Independent testing by fluorescence in situ hybridization confirmed the presence of NUTM1 and partner gene rearrangement. This study establishes that NUT-associated tumors transgress the midline and account for a subset of primitive neoplasms occurring in soft tissue and viscera. Tumors harboring NUTM1 gene fusions are presumably underrecognized, and the extent to which they account for undifferentiated mesenchymal, neuroendocrine, and/or epithelial neoplasms is unclear. Moreover, the relationship, if any, between NUT-associated tumors in soft tissue and/or viscera, and conventional NUT carcinoma, remains to be elucidated. © 2018 Wolters Kluwer Health, Inc. All rights reserved. |
| Keywords: | nut midline carcinoma; brd4; fusions; bcorl1; brd3; mxd1; nutm1 |
| Journal Title: | American Journal of Surgical Pathology |
| Volume: | 42 |
| Issue: | 5 |
| ISSN: | 0147-5185 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2018-05-01 |
| Start Page: | 636 |
| End Page: | 645 |
| Language: | English |
| DOI: | 10.1097/pas.0000000000001021 |
| PROVIDER: | scopus |
| PMCID: | PMC5893407 |
| PUBMED: | 29356724 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2018 -- Source: Scopus |
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