New Research Enhances Diagnostic Accuracy for NUT Carcinoma

Recent research from the Dana-Farber Cancer Institute has illuminated critical gaps in the diagnosis of NUT carcinoma, an aggressive form of cancer that primarily affects the lungs, head, and neck. The study, published on July 24, 2025, in the peer-reviewed journal Clinical Cancer Research, finds that standard DNA-based testing often fails to detect this malignancy, leading to a substantial rate of underdiagnosis among patients.

NUT carcinoma is characterized by gene fusions involving the NUTM1 gene, which can result in the production of malfunctioning proteins. According to Dr. Jia Luo, co-senior author of the study and a thoracic oncologist at the Lowe Center for Thoracic Oncology at Dana-Farber, “More than 75% of patients with NUT carcinoma may remain undiagnosed because current DNA tests do not effectively identify these gene fusions.” This assertion underscores the need for improved diagnostic protocols that go beyond traditional methods.

The research highlights the efficacy of several advanced testing methods, including NUT immunohistochemistry (IHC), RNA fusion testing, and NUTM1 fluorescence in situ hybridization (FISH). These techniques demonstrated markedly higher detection rates for NUT carcinoma fusions—100%, 84%, and 92%, respectively—compared to less than 25% for standard DNA sequencing and circulating tumor DNA (ctDNA) testing. Dr. Luo emphasized the necessity of consulting pathology specialists to ensure the implementation of these advanced tests when NUT carcinoma is suspected.

The median survival rate for patients diagnosed with NUT carcinoma is alarmingly low, at just 6.7 months, which emphasizes the importance of early and accurate diagnosis. “If a diagnosis of NUT carcinoma is being considered, clinicians should utilize more definitive tests to guide appropriate treatment and access to clinical trials,” Dr. Luo stated.

In their comprehensive analysis, Dr. Luo and co-senior author Dr. Christopher French of Brigham and Women's Hospital evaluated molecular testing results from 116 tumors presumed to be NUT carcinoma. Their findings revealed that many tumors lacked additional mutations commonly associated with other cancers, yet some did contain mutations related to epigenetic, cell cycle, and DNA repair pathways. This insight could pave the way for developing targeted combination therapies in the future.

The study builds upon earlier work that characterized NUT carcinoma as a subtype of squamous cell carcinoma, as detailed in an article by Luo and colleagues published earlier in Nature Reviews Clinical Oncology. The research team has initiated laboratory studies to explore whether targeting specific mutations could enhance patient outcomes.

This research is crucial not only for improving diagnostic accuracy but also for informing treatment strategies for those affected by this aggressive cancer. As noted by Dr. Luo, “These findings warrant immediate change to the diagnostic workflow for patients with suspected NUT carcinoma.” The implications of this study may significantly alter the standard of care in oncology for patients facing this rare but devastating disease, ultimately leading to enhanced survival rates and better quality of life for those diagnosed.