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case_images: Timeline of clinical treatment course and radiologic features. (A) Computed tomography (CT) scan of mediastinal lymph nodes at baseline. (B) CT scan of lung masses at baseline. (C) CT scan of mediastinal lymph nodes after 18 days of crizotinib treatment. (D) CT scan of lung masses after 18 days of crizotinib treatment. (E) CT scan of mediastinal lymph nodes after 12.5 months of crizotinib treatment. (F) CT scan of lung masses after 12.5 months of crizotinib treatment. (G) CT scan of mediastinal lymph nodes after 14 months of crizotinib treatment. (H) CT scan of lung masses after 14 months of crizotinib treatment. (I) CT scan of mediastinal lymph nodes after 17 months of crizotinib treatment. (J) CT scan of lung masses after 17 months of crizotinib treatment. (K) Timeline of the patient's clinical treatment course and response to cancer drugs during the patient's clinical course. Red arrows indicate the tumor and lymph node sites. (L) Pathological examination of the patient tumor tissue. Hematoxylin and eosin (HE) staining of the biopsy specimen showed a poorly differentiated tumor tissue. IHC experiments showed positive expressions of Ki-67, Napsin A, TTF-1, and negative expression of P40 (x200), revealing an adenocarcinoma origin of the lung cancer.
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case_images: Multiple nodules were found in both lungs, accompanied by enlarged right hilar and mediastinal lymph nodes, and right pleural effusion with adjacent lung parenchyma insufficiency (Figure 1A). The size of the target lesion in the lower right lobe is about 7.0x6.0cm (Figure 1B). After 18 days of the treatment with crizotinib, mediastinal lymph nodes are reduced (Figure 1C). Lung lesions are also reduced (Figure 1D). At the time of 12.5 months of crizotinib treatment, hilar lymph nodes decreased (Figure 1E), and the pleural effusion decreased (Figure 1F). After 14 months of crizotinib treatment, mediastinal lymph nodes changed (Figure 1G) and the right pleural effusion increased (Figure 1H). After 17 months of oral crizotinib, the mediastinal lymph nodes were enlarged (Figure 1I). The left pleural effusion was significantly increased (Figure 1J). The pathological results changed by the timeline of medication (Figure 1K). Metastatic carcinoma of the right parietal pleura combined with the source of immunohistochemical lung adenocarcinoma was diagnosed (Figure 1L). Based on the identification of this new ROS1 fusion, from December 30, 2019, the patient took crizotinib twice a day at a dose of 250 mg (Figure 1K). After 18 days of the treatment with crizotinib, the lesions in both lungs and mediastinum were reduced (Figure 1C and D). PR was achieved after 12.5 months crizotinib treatment, the imaging map showed that the target lesion was a cord-like high-density shadow, the amount of pleural effusion was reduced, and the hilar lymph nodes were reduced (Figure 1E and F). After 14 months of oral administration of crizotinib, the right pleural effusion increased and the lesion was evaluated as stable disease (SD) (Figure 1G and H). Finally, after 17 months of oral crizotinib, the target lesion was about 2.6 cm x 2.0 cm in the right lower hilum, and the left pleural effusion was significantly increased, and the lesion was PD (Figure 1I and J).
case_images: Identification and verification of a novel BAIAP2-ROS1 fusion. (A) DNA sequencing reads indicating BAIAP2 and ROS1 fusion regions were visualized by the Integrative Genomic Viewer (IGV) software. The fusion breakpoints are localized at chr17: q23: 79,082,614 and chr6: q22.1: 117,644,699, respectively. (B) RNA sequencing reads indicating BAIAP2 and ROS1 fusion regions were visualized by the Integrative Genomic Viewer (IGV) software. The fusion breakpoints are localized at chr17: q23: 79,082,304 and chr6: q22.1: 117,641,192, respectively. (C) Schematic of genomic rearrangement involving the fusion breakpoints in mRNA and protein level. The transcript resulted in exons 1-13 of BAIAP2 containing coiled-coil domains fused to exons 35-43 of ROS1 including kinase domain. Pink, BAIAP2; Blue, ROS1; IMD, IRSp53 and MIM (missing in metastases) homology Domain.
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case_images: Sequences support of BAIAP2-ROS1 fusion was detected by DNA-Seq (Figure 2A) and RNA-Seq (Figure 2B) methods. Schematic of genome rearrangement of BAIAP2-ROS1 involving fusion breakpoints at mRNA and protein levels (Figure 2C). The fusion of BAIAP2-ROS1 in tissue was determined which was formed by exon1-exon13 fragment of BAIAP2 and exon35-exon43 fragment of ROS1 (Figure 2A and C). The rearrangement was further verified by RNA fusion plate hybrid capture sequencing (Berry Oncology Corporation) technology to confirm the existence of BAIAP2-ROS1 (B13: R36) fusion mutation (Figure 2B and C).