Journal article

A MXI1-NUTM1 fusion protein with MYC-like activity suggests a novel oncogenic mechanism in a subset of NUTM1-rearranged tumors

CR McEvoy, H Holliday, N Thio, C Mitchell, DY Choong, B Yellapu, HS Leong, H Xu, S Lade, J Browning, EA Takano, DJ Byrne, AJ Gill, CP Duong, J Li, AP Fellowes, SB Fox, A Swarbrick, OWJ Prall

Laboratory Investigation | ELSEVIER SCIENCE INC | Published : 2021

Abstract

Most NUTM1-rearranged neoplasms (NRNs) have fusions between NUTM1 and BRD (bromodomain-containing) family members and are termed NUT carcinomas (NCs) because they show some squamous differentiation. However, some NRNs are associated with fusions between NUTM1 and members of the MAD (MAX dimerization) gene family of MYC antagonists. Here we describe a small round cell malignancy from the gastro-esophageal junction with a previously unreported fusion between NUTM1 and the MAD family member MXI1. In contrast to NCs, the MXI1-NUTM1 tumor did not show squamous differentiation and did not express MYC, TP63 or SOX2, genes known to be targets of BRD-NUTM1 proteins and critical for NC oncogenesis. Tr..

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Grants

Awarded by National Health and Medical Research Council


Funding Acknowledgements

The authors wish to acknowledge Tim Semple, David Yoannidis, and Gisela Mir Arnau for performing RNAseq, and Anna Korczynski for technical assistance. Tumor profiling at Peter Mac is made possible by the generous support of the Peter MacCallum Foundation. SBF is funded by an NHMRC Practitioner Fellowship APP1079329.