Primary malignant epithelioid and rhabdoid tumor of bone harboring ZNF532-NUTM1 fusion: the expanding NUT cancer family
Journal
Genes Chromosomes and Cancer
Journal Volume
58
Journal Issue
11
Pages
809-814
Date Issued
2019
Author(s)
Abstract
NUTM1 gene rearrangement is the genetic hallmark of NUT carcinoma, an aggressive tumor that most commonly affects the thoracic and head and neck regions and often exhibits squamous differentiation. The most common fusion partner gene is BRD4, followed by BRD3 and NSD3. Recently, NUTM1 gene rearrangement has been identified in rare tumors from soft tissues, intracranial locations, and other visceral organs. These tumors often show high grade malignant epithelioid to round cell histomorphology and lack evidence of squamous and/or epithelial differentiation. Therefore, their relationship with classic NUT carcinoma is still uncertain. Here, we present a primary mandible bone tumor of a 21-year-old female exhibiting monotonous epithelioid and rhabdoid cytomorphology, vesicular chromatin, and prominent nucleoli. The initial immunohistochemical workup was non-specific, showing only CD34 positivity while being negative for cytokeratin (AE1/AE3), EMA, p63, etc. INI-1 expression was retained. RNA sequencing was performed and identified a rare ZNF532-NUTM1 gene fusion, which had only been reported in a single case of pulmonary NUT carcinoma. The fusion was confirmed by FISH for NUTM1 gene rearrangement and supported by diffuse and strong NUT immunoreactivity. MYC mRNA up-regulation and immunoreactivity, a common finding in NUT carcinoma, was also observed in this tumor, suggesting a possible common pathogenetic mechanism and potential treatment target. The patient presented with a non-metastatic disease status and received hemimandibulectomy, selective neck dissection (level Ib), and post-operative radiation therapy. She remained disease free 3.6 years after the initial diagnosis. ? 2019 Wiley Periodicals, Inc.
Subjects
bone tumor; NUT carcinoma; NUTM1; rhabdoid; ZNF532
SDGs
Other Subjects
CD34 antigen; cell cycle protein; nuclear protein; NUTM1 protein, human; oncoprotein; transcription factor; tumor marker; tumor protein; zinc finger protein; adjuvant radiotherapy; adult; Article; case report; clinical article; female; fibula graft; fluorescence in situ hybridization; fusion gene; gene; gene fusion; gene rearrangement; histopathology; human; human tissue; immunohistochemistry; mandible resection; mandible tumor; neck dissection; nuclear magnetic resonance imaging; NUTM1 gene; oncogene myc; priority journal; rhabdoid tumor; RNA sequence; surgical margin; young adult; ZNF532 NUTM1 fusion gene; bone tumor; carcinoma; genetics; mandible; rhabdoid tumor; sarcoma; sequence analysis; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Cell Cycle Proteins; Female; Gene Fusion; Gene Rearrangement; Humans; In Situ Hybridization, Fluorescence; Mandible; Neoplasm Proteins; Nuclear Proteins; Oncogene Proteins, Fusion; Rhabdoid Tumor; Sarcoma; Sequence Analysis, RNA; Transcription Factors; Young Adult; Zinc Fingers
Publisher
Blackwell Publishing Inc.
Type
journal article