2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.55 Molecular characterization of NUT carcinoma: A report from the NUT carcinoma registry

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The report presents an analysis of NUT carcinoma (NC), a rare and underdiagnosed type of squamous cell cancer characterized by NUTM1 gene fusions, which are essential for its pathogenesis. The study was compiled from the NUT carcinoma registry, involving patients whose tumors underwent next-generation sequencing (NGS) to identify genetic mutations, particularly focusing on NUTM1 fusions.<br /><br />The study highlights that standard DNA NGS assays detect only 22% of NUT carcinomas, a detection rate that has not improved over time. In contrast, RNA-based fusion tests or NUT immunohistochemistry (IHC)/fluorescence in situ hybridization (FISH) happen to be more reliable. An emphasis is placed on incorporating these tests into routine diagnostics for suspected NC cases.<br /><br />The analysis demonstrates that NUT carcinomas often feature additional alterations in genes associated with epigenetic regulation, DNA repair, and cell cycle control, suggesting these pathways warrant further investigation for therapeutic targeting.<br /><br />The cohort included 116 patients with available NGS data, revealing a median age of 37.5 years, with a slight male predominance (59.5%). Notably, this cancer type affects both smokers and non-smokers, as a significant proportion of patients had no smoking history.<br /><br />Among the fusion partners for NUTM1, BRD4 was the most prevalent, followed by non-BRD4 partners such as BRD3 and NSD3, highlighting the genetic diversity within NC. Additionally, there was significant variation in PD-L1 expression and tumor mutation burden across the cohort, which are potential biomarkers of therapeutic response.<br /><br />The study advocates for broader adoption of RNA fusion testing and utilization of NUT IHC/FISH techniques in clinical practice to improve the diagnostic yield for this aggressive cancer, given the low detection rate of standard DNA NGS. Consistent funding from various sources underscores the importance of continued research in developing better diagnostic and treatment strategies for NUT carcinoma.

Asset Subtitle

Justin Kim

Keywords

NUT carcinoma

NUTM1 gene fusions

next-generation sequencing

RNA fusion testing

NUT immunohistochemistry

fluorescence in situ hybridization

epigenetic regulation

BRD4

PD-L1 expression

tumor mutation burden