LMNA::NTRK1 Fusion-positive Leiomyosarcoma: Discrepancy between DNA-based Comprehensive Genomic Profiling and RNA Sequencing

Norito Suzuki; Masashi Idogawa; Makoto Emori; Kazuyuki Murase; Yohei Arihara; Hajime Nakamura; Makoto Usami; Tomohiro Kubo; Ichiro Kinoshita; Shintaro Sugita; Takashi Tokino; Tadashi Hasegawa; Akihiro Sakurai; Kohichi Takada

doi:10.2169/internalmedicine.2879-23

LMNA::NTRK1 Fusion-positive Leiomyosarcoma: Discrepancy between DNA-based Comprehensive Genomic Profiling and RNA Sequencing

Intern Med. 2023 Dec 18. doi: 10.2169/internalmedicine.2879-23. Online ahead of print.

Authors

Affiliations

¹ Department of Medical Oncology, Sapporo Medical University School of Medicine, Japan.
² Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Japan.
³ Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
⁴ Division of Clinical Cancer Genomics, Hokkaido University Hospital, Japan.
⁵ Department of Surgical Pathology, Sapporo Medical University School of Medicine, Japan.
⁶ Department of Medical Genetics and Genomics, Sapporo Medical University School of Medicine, Japan.

PMID: 38104989
DOI: 10.2169/internalmedicine.2879-23

Abstract

A 26-year-old man presented with a tumor in the left soleus muscle. The tumor was diagnosed as a locally advanced leiomyosarcoma. The patient was treated with irradiation followed by wide resection. One year after surgery, the patient presented with multiple lung metastases. Despite aggressive sequential chemotherapy, systemic metastatic tumors continued to develop. To explore therapeutic options for the patient, we performed DNA-based CGP with FoundationOne^® CDx (F1). F1 identified anout-of-strand rearrangement of the NOS1AP::NTRK1 gene, which has not been previously reported. In contrast, RNA sequencing revealed an in-frame LMNA::NTRK1 gene, which is an oncogenic fusion gene.

Keywords: Leiomyosarcoma; NTRK fusion gene; RNA sequencing.