PMC6890554_01
Computed tomography (CT) and Hematoxylin & eosin (HE) staining for the lesion in right lower lobe (A,B) and left upper lobe (C,D) showed both of the tumors are well-differentiated adenocarcinomas. The right one has papillary-predominant pattern, and the left one appeared with acinar-predominant and lepidic pattern. Red arrows point the tumor sites.
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F1
ADCs in the right lower and the left upper lobes in August, 2018 (Figure 1). After surgical resection of the two primary ADCs, the patient was initially treated with three cycles of pemetrexed (800 mg/m2 d1), followed by pemetrexed 800 mg/m2 d1 plus bevacizumab 300 mg/m2 d1 for one cycle.
Concomitant EML4-ALK fusion or TPM3-ROS1 fusion were found in each ADC. (A,B) Showed the fusion breakpoints detected by targeted NGS and alterations in gene, mRNA and protein level caused by two fusions, respectively. NGS sequencing reads indicating fusion regions were demonstrated by Integrative Genomics Viewer (IGV) software. CC, coiled-coil domain.
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F2
ROS1 (Figure 2B). RNA-seq was conducted to further confirm the expression of EML4-ALK and TPM3-ROS1 fusions at mRNA level (Figure 2). These two fusion proteins contain the N-terminal coiled-coil domain of the 5' partner gene and the C-terminal tyrosine kinase domain of ALK or ROS1, which could mediate the full kinase function and result in constitutive kinase activity and oncogenic transformation (Figure 2).
PMC6890554_02