NUT midline pulmonary carcinoma - molecular profiling of three cases and a literature review of the per-spectives for precision oncology
Abstract
NUT midline pulmonary carcinoma - molecular profiling of three cases and a literature review of the per-spectives for precision oncology
Background: Mediastinal malignancies in young adults should be treated as effectively as possible. Currently applied morphologic and laboratory diagnostic procedures can lead to inconclusive results. Rapid and accurate solutions in such cases can be achieved by incorporating next-generation sequencing (NGS) tests into the diagnostic algorithm, as we demonstrate in our three cases. The application of precision oncology principles and targeted therapy may lead to better prognosis in the near future.
Material and methods: Three patients with NUT midline carcinoma (NMC) were diagnosed and treated in our hospital. Molecular profiling of tumor tissue was performed using the FusionPlex Archer Solid Tumor Kit (ArcherDX Inc.) and TST170/TSO500 assay (Illumina). In addition, a literature review was conducted to provide insights into the molecular mechanisms of NMC development and ongoing clinical trials with targeted therapy.
Results: Case 1: Patient 1, a 26-year-old female non-smoker with stage IV suspected non-small cell cancer of the right lung, achieved partial remission on paclitaxel-carboplatin-bevacizumab therapy. NGS revealed BRD4-NUTM1 fusion transcript, conclusive for NMC, and also high tumor mutation burden (TMB).
Case 2: Patient 2, a 20-year-old male non-smoker, was examined for large left-sided pulmonary tumor of similar morphology. After chemotherapy with etoposide, carboplatin and ifosfamide, partial remission was observed. The patient died six months after diagnosis. NGS revealed NSD3-NUTM1 gene fusion transcript, conclusive for NMC, and also high TMB.
Case3: Patient 3, a 42-year-old male non-smoker was diagnosed with large left-sided pulmonary tumor of simi-lar morphology. Chemotherapy with etoposide, carboplatin and paclitaxel with carboplatin resulted in short-las-ting transient improvement, but the patient died six weeks after diagnosis. NGS revealed BRD4-NUTM1 fusion transcript. TMB could not be analyzed.
Conclusions: Histopathology combined with molecular profiling of the tumor has the potential to become a va-luable tool for precise diagnosis of mediastinal cancers. The application of precision oncology principles and the use of experimental therapy in ongoing clinical trials (e.g. BET and HDAC inhibitors) may improve the prognosis of patients with NMC.