NUTM2B (NUT Family Member 2B)

Despite the relatively favorable outcomes in BCOR sarcomas, the relapse rate is considerable, whereas pediatric patients with CIC sarcoma typically develop metastatic disease and have poor outcomes. The data provide a prospective foundation for genetically based therapeutic strategies and risk stratification.

This case, combined with others, reveals a potential pattern of central nervous system (CNS) metastasis within this molecular subgroup, thus highlighting the importance of brain surveillance imaging and the relevance of CNS-penetrant chemotherapy-based regimens.

This study introduces a novel salivary and lung tumor entity driven by NFATC2::NUTM2A/B fusions and displaying myoepithelial-like morphology but imperfect myoepithelial immunophenotype. Report of more cases should shed light on the biological properties and appropriate therapeutic strategies of this novel neoplasm.

ESR1 expression was significantly higher in NUTM1/NUMT2B-rearranged intra-abdominal sarcomas. NUTM1/2B-rearranged intra-abdominal sarcomas herein represent an emerging entity distinct from the sarcomatous lineage at the transcriptomic level, and characterized by its overexpression of estrogen receptors, which could be an indication for another therapeutic option.

Our results further support the existence of primary cutaneous NAC and suggest that it may represent an entity distinct from extracutaneous NUT carcinoma.

A positive RNA-seq or methylation array analysis result may be sufficient evidence for a diagnosis of CIC-RS in the appropriate histologic context. A negative or inconclusive/unclassified RNA-seq or methylation array analysis result in a tumor with high initial suspicion for CIC-RS likely requires careful reevaluation.

Functional rescue assays suggest that BMPR1A is a critical mediator of the oncogenic role of m6A-methylated NUTM2B-AS1 in HCC. METTL3- and METTL16-mediated m6A methylation of NUTM2B-AS1 is a novel oncofetal molecular event in HCC that promotes HCC stemness via epigenetically activating BMPR1A transcription.

These findings broaden the current spectrum of gene rearrangements in head and neck carcinomas and support the utility of clinical NGS in identifying unusual, actionable alterations in diagnostically challenging cases.

In the latter subgroup, four novel fusion transcripts were found for which the clinical relevance remains unclear: NAB2::NCOA2, YAP1::NUTM2B, HSPA8::BRAF, and PDE2A::PLAG1. Overall, targeted RNA-seq has proven extremely valuable in the diagnostic workflow of soft tissue and bone tumours.

This may be related to the known molecular relationship between KDM2B and BCOR in the polycomb repressive complex 1.1. Immunohistochemical analysis of KDM2B is a potentially valuable diagnostic tool for BCOR-associated sarcomas, including those with KDM2B rearrangement.