Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

NUTM1-Rearranged Neoplasms: A Heterogeneous Group of Primitive Tumors with Expanding Spectrum of Histology and Molecular Alterations: An Updated Review

Version 1 : Received: 29 September 2021 / Approved: 29 September 2021 / Online: 29 September 2021 (12:17:31 CEST)

A peer-reviewed article of this Preprint also exists.

Luo, W.; Stevens, T.M.; Stafford, P.; Miettinen, M.; Gatalica, Z.; Vranic, S. NUTM1-Rearranged Neoplasms: A Heterogeneous Group of Primitive Tumors with Expanding Spectrum of Histology and Molecular Alterations: An Updated Review. Curr. Oncol. 2021, 28, 4485-4503. Luo, W.; Stevens, T.M.; Stafford, P.; Miettinen, M.; Gatalica, Z.; Vranic, S. NUTM1-Rearranged Neoplasms: A Heterogeneous Group of Primitive Tumors with Expanding Spectrum of Histology and Molecular Alterations: An Updated Review. Curr. Oncol. 2021, 28, 4485-4503.

Abstract

Nuclear protein of testis (NUT), a protein product of the NUTM1 gene (located on the long arm of chromosome 15) with highly restricted physiologic expression in post-meiotic spermatids, is the oncogenic driver of a group of emerging neoplasms when fused with genes involved in transcription regulation. Although initially identified in a group of lethal midline carcinomas in which NUT forms fusion proteins with bromodomain proteins, NUTM1-rearrangement has since been identified in tumors at non-midline locations, with non-bromodomain partners and with varied morphology. The histologic features of these tumors have also expanded to include sarcoma, skin adnexal tumors, and hematologic malignancies that harbor various fusion partners and are associated with markedly different clinical courses varying from benign to malignant. Most of these tumors have nondescript primitive morphology and therefore should be routinely considered in any undifferentiated neoplasm. The diagnosis is facilitated by the immunohistochemical use of the monoclonal C52 antibody, fluorescence in situ hybridization (FISH), and, recently, RNA-Sequencing. The pathogenesis is believed to be altered expression of oncogenes or tumor suppressor genes by NUT-mediated genome-wide histone modification. NUTM1-rearranged neoplasms respond poorly to classical chemotherapy and radiation therapy. Targeted therapies such as bromodomain and extraterminal domain inhibitor (BETi) therapy are being developed. This current review provides an update of NUTM1-rearranged neoplasms, focusing on the correlation between basic sciences and clinical aspects.

Keywords

NUTM1 gene; NUT protein; Neoplasms; Pathogenesis; Therapy

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.