• Tian Luo, Wentao Ji, Weihong Guo, Dandan Zhang, Jianping Liang, and Yanhua Lv.
• Zhongshan City People's Hospital, Xinxiang Medical University, Xinxiang, Henan, China.
• Medicine (Baltimore). 2025 Jan 24; 104 (4): e41350e41350.

RationaleROS proto-oncogene 1 (ROS1) fusion is a rare but important driver mutation in non-small cell lung cancer, which usually shows significant sensitivity to small molecule tyrosine kinase inhibitors. With the widespread application of next-generation sequencing (NGS), more fusions and co-mutations of ROS1 have been discovered. Non-muscle myosin heavy chain 9 (MYH9) is a rare fusion partner of ROS1 gene as reported. Here, we report an even rare case with coexistence of short and long variants MYH9-ROS1 fusions at the RNA level accompanied by TP53 mutation, insensitively to antitumor therapy.Patient Concerns And DiagnosisA 37-year-old nonsmoking man was diagnosed with stage IVB (T4N3M1c) lung adenocarcinoma. The tumor was identified to have MYH9 (exon 37)-ROS1 (exon 35) rearrangement with TP53 mutation at the DNA level by DNA-NGS analysis of lymph node biopsy tissue in March 2023. Interestingly, it was transcribed into coexistence of short and long variants MYH9-ROS1 (M36, R36) and MYH9-ROS1 (M36, R35) fusions at RNA level by RNA-NGS analysis.InterventionsFirst-line tyrosine kinase inhibitors crizotinib was given firstly, showing partial response (PR) but significant progression within 3 months. To determine the resistance mechanism to crizotinib and the genetic variation, DNA-NGS and RNA-NGS were performed again on a new biopsy tissue of lymph node in August 2023.OutcomesRare coexistence of short and long variants of MYH9-ROS1 fusions was identified again, but the typical mechanisms of crizotinib resistance were not observed. Switching to lorlatinib resulted in brief PR about 2 months. Subsequent 2 courses of system chemotherapy provided short-term PR less than 2 months. The patient died with a total survival of 10 months.LessonsWe must pay attention to rare dual short and long variants of the MYH9-ROS1 fusions, it may affect the efficacy of ROS1-tyrosine kinase inhibitors targeted therapy.Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.

25 keywords...

hide…