Advances in Diagnosing and Treating NUT Carcinoma: New Insights from Dana-Farber Study

A recent groundbreaking study conducted by researchers at Dana-Farber Cancer Institute has revealed crucial advancements in the diagnosis and treatment of NUT carcinoma, an aggressive and often underdiagnosed cancer. NUT carcinoma is characterized by gene fusions involving the NUTM1 gene, leading to the formation of a malfunctioning fusion protein. This cancer predominantly affects young individuals with little to no smoking history, and its presentation often overlaps with other squamous cell carcinomas, complicating diagnosis.

The study, published in Clinical Cancer Research, analyzed molecular test results from 116 tumors suspected of NUT carcinoma. It demonstrated that standard DNA-based testing methods detect NUT gene fusions in less than 25% of cases, which contributes to the potential underdiagnosis of this lethal cancer with a median survival of just 6.7 months.

More reliable diagnostic techniques, such as NUT immunohistochemistry (IHC), RNA fusion testing, and NUTM1 FISH, showed significantly higher detection rates—up to 100%, 84%, and 92%, respectively. This highlights the importance of employing these methods when NUT carcinoma is suspected, especially considering that early detection is vital for effective treatment and enrollment in clinical trials.

The research also shed light on the genetic landscape of NUT carcinoma, revealing that many cases lack additional mutations, though some exhibit mutations linked to epigenetic regulation, cell cycle, or DNA repair pathways. Understanding these mutations could open new avenues for targeted therapies.

In addition to diagnostic improvements, the study underscores the necessity of integrating RNA fusion testing alongside DNA testing to accurately identify NUT gene fusions. This approach mirrors protocols used in other cancers where gene fusions are key diagnostic markers.

Early diagnosis is especially crucial because NUT carcinoma often involves the lungs, head, or neck, and may be suspected in younger patients with poorly differentiated tumors. The study’s authors emphasize that recognizing these features and utilizing the most precise testing methods can significantly impact patient outcomes.

For clinicians managing suspected cases of lung, head, or neck cancer, incorporating specific gene fusion tests like NUT IHC, RNA testing, and FISH is recommended to improve diagnostic accuracy. Laboratory studies are ongoing to explore targeted treatment options for mutations identified in the tumor genome, potentially offering new hope for patients with this aggressive disease.

This research underscores a vital shift in diagnosing NUT carcinoma, promoting tailored testing and early intervention to improve prognosis for affected patients.

(source: https://medicalxpress.com/news/2025-07-paves-path-diagnosis-treatment-nut.html)