PMC9548572_01
Patient CT images. CT scans of lesion 1 (A-C) and lesion 2 (D-F) in lung as well as lesion in liver (G-I) before and after 1 or 2 months of pralsetinib treatment.
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Computed tomography (CT) scan revealed two space-occupying lesions in the lower lobe of the right lung and diffuse hepatic metastases ( Figures 1A, G ). After a month, the CT findings showed shrinkage of the lung lesions by 36.11% and 37.5% ( Figures 1A, B, D, E ) and reduction of the liver lesions by 18.68% ( Figures 1G, H ). One month later, the decreases in tumor size of 13.04% and 6.7% in lung as well as 21.62% in liver were shown on CT ( Figures 1C, F, I ).
NGS and FISH findings. (A) NGS analysis showing a breakpoint of the MIR4299/MIR8070-RET fusion and their sequence information. (B) Schematic diagram of the MIR4299/MIR8070-RET fusion. (C) FISH results showing the RET signal. FISH tests on lung biopsy tissue from the patient revealed more than 60% tumor content. FISH with RET dual color break-apart probe. The red signal represents the 5' end RET gene while the green signal represents the 3' end RET gene. The signal separated red and green signals, consistent with RET fusion. In most cases, the red signal and green signal were synchronized in clusters, and RET gene amplification could be confirmed by combining microscopic observation. Yellow represents red and green signals superimposed. In addition, the amplified signal (yellow signal, or clusters of red-green signal) is too strong, which obscures the fusion signal. (D) The image of negative control showing each color probe without fusion gene or amplification.
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RET fusion and amplification ( Figure 2C ). The fusion encompassed MIR4299/MIR8070 intergenic region and exons 3 to 20 of RET, holding the whole RET kinase domain, which has never been reported before. RT-PCR was not performed since the tumor tissues were immersed in formalin, which caused serious degradation of RNA, but this degradation did not affect FISH results.