PMC10157030_01
Treatment milestones of our case. (A) treatment timeline of the case; (B) CT scans of the left upper lobe mass, mediastinal pleural nodule, and pleural effusion at baseline; (C) CT scans of the left upper lobe mass, mediastinal pleural nodule, and pleural effusion at the first follow-up after treatment; (D) CT scans of the left upper lobe mass, mediastinal pleural nodule, and pleural effusion at the second follow-up after treatment; (E) CT scans of the left upper lobe mass, mediastinal pleural nodule, and pleural effusion at the third follow-up after treatment LUAD, lung adenocarcinoma; CT, computed tomography; LDLR, low-density lipoprotein receptor; ROS1, ROS proto-oncogene 1; PR, partial response.
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Lung adenocarcinoma was confirmed by pleural effusion cytology after closed thoracic drainage ( Figure 1A ). After admission, the patient underwent further examinations as follows: 1) the specific tumor marker carcinoembryonic antigen (CEA) level was normal (3.52 microg/L); 2) an enhanced CT scan further revealed a mass in the left upper lobe of the lung and left pleural thickening with nodular formation ( Figure 1B ); 3) magnetic resonance imaging (MRI) of the head revealed no obvious abnormality; 4) single photon emission CT/CT (SPECT/CT) scan exhibited no bone metastasis. Criteria in Solid Tumors (RECIST 1.1). Chest CT scan revealed that left lobe mass and mediastinal pleural nodules reduced, and pleural effusion was absorbed, indicating that this patient achieved partial response (PR) ( Figure 1C ). In January 2022, the chest CT scan demonstrated that the lesion shrank further, pleural effusion continued to decrease, and PR was noted ( Figure 1D ). Another chest CT scan conducted in December 2022 demonstrated that the lesion shrank further, pleural effusion elementally disappeared, and the treatment showed PR ( Figure 1E ).
Identification and verification of LDLR-ROS1 fusion in this case. (A) RNA sequencing reads indicating visualization of the LDLR and ROS1 fusion regions using the Integrative Genomics Viewer (IGV) software. The fusion breakpoints are localized at chr19: p13.2: 11,212,559 and chr6: q22.1: 117,646,031, respectively; (B) Schematic of genomic rearrangement involving the fusion breakpoints at mRNA and protein levels; the transcript resulted in exons 1-2 of LDLR fused to exons 34-43 of ROS1, including kinase domain. LDLR, low-density lipoprotein receptor; ROS1, ROS proto-oncogene 1; Orange color represents LDLR; Blue color represents ROS1; KD, kinase domain; e, exon.
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Besides, an RNA fusion panel based on amplicon sequencing (Berry Oncology Corporation, Beijing, China) was also used to verify this fusion variant from total RNA which isolated from FFPE tissues. Both the DNA and RNA-based sequencing technology revealed LDLR exon 2-ROS1 exon 34 rearrangement in the tissue ( Figure 2 ).