1.Cancer-Specific Sequences in the Diagnosis and Treatment of NUT Carcinoma
Mi-Sook LEE ; Sungbin AN ; Ji-Young SONG ; Minjung SUNG ; Kyungsoo JUNG ; Eun Sol CHANG ; Juyoung CHOI ; Doo-Yi OH ; Yoon Kyung JEON ; Hobin YANG ; Chaithanya LAKSHMI ; Sehhoon PARK ; Joungho HAN ; Se-Hoon LEE ; Yoon-La CHOI
Cancer Research and Treatment 2023;55(2):452-467
Purpose:
NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC.
Materials and Methods:
We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts.
Results:
As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness.
Conclusion
This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.
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