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NUTM1 Gene Fusions Characterize a Subset of Undifferentiated Soft Tissue and Visceral Tumors.
- Source :
-
The American journal of surgical pathology [Am J Surg Pathol] 2018 May; Vol. 42 (5), pp. 636-645. - Publication Year :
- 2018
-
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.
- Subjects :
- Adult
Aged
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors genetics
Biomarkers, Tumor analysis
Cell Cycle Proteins
Child, Preschool
Female
Genetic Predisposition to Disease
High-Throughput Nucleotide Sequencing
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Male
Middle Aged
Phenotype
RNA-Binding Proteins genetics
Repressor Proteins genetics
Retrospective Studies
Sequence Analysis, RNA methods
Soft Tissue Neoplasms chemistry
Soft Tissue Neoplasms pathology
Transcription Factors genetics
Biomarkers, Tumor genetics
Cell Differentiation
Gene Fusion
Neoplasm Proteins genetics
Nuclear Proteins genetics
Soft Tissue Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-0979
- Volume :
- 42
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- The American journal of surgical pathology
- Publication Type :
- Academic Journal
- Accession number :
- 29356724
- Full Text :
- https://doi.org/10.1097/PAS.0000000000001021