YO20 - In-depth analysis of unknown NTRK1-fusion gene detected in DNA-based comprehensive genomic profiling.

Case summary

In-depth analysis of unknown NTRK1-fusion gene detected in DNA-based comprehensive genomic profiling.

[Background] The use of neurotrophic tropomyosin receptor kinase (NTRK) inhibitors yields excellent clinical outcomes in NTRK fusion–positive tumors. These compounds can be administered based on the results of DNA sequencing, such as comprehensive genomic profiling (CGP). Here, we present a patient with a leiomyosarcoma (LMS) that harbored an NTRK fusion gene, in which the result of DNA-based CGP differed from that of RNA sequencing.

[Case Presentation] A 26-year-old man had developed a tumor in the left soleus muscle. The tumor was diagnosed as a locally advanced LMS according to radiological and pathological findings. The patient was treated with irradiation followed by wide resection. A year after surgery, the patient presented with multiple lung metastases. To explore suitable therapeutic options, we carried out DNA-based CGP with FoundationOne® CDx (F1) using a resected primary tumor. F1 identified an out-of-strand rearrangement for the NOS1AP::NTRK1 gene, which has not been previously reported. To capture the pathogenesis of the unknown fusion gene, we performed RNA sequencing. However, it revealed an in-frame LMNA::NTRK1 gene, which differed from the DNA-based CGP result and was characterized as an oncogenic fusion gene. To rule out the possibility of sequence error regarding F1, we also carried out PCR and Sanger sequencing by using genomic DNA. Finally, we determined the putative NTRK1 rearranged gene which has a discrepancy between genomic DNA and mRNA because of introns.

[Conclusion] When DNA-based CGP detects a variant of a fusion gene of uncertain significance, RNA sequencing is a more reliable diagnostic tool in decision-making in treatments for solid tumors.

Clinical trial identification

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