case_images: PMC7234975_01
case_images: Clinical course and representative clinical images of the patient with NSCLC.. Notes: (A) Patient's treatment timeline showed the application of different drug treatments. (B) CT scan images were taken during baseline of cancer diagnosis, the GP regimen/recombinant human endostatin (Endostar) combinational treatment, and the PP regimen/bevacizumab combinational treatment, respectively. (C) CT scan images were taken during oral crizotinib treatment, and oral alectinib treatment, respectively. (D) Map of clonal evolution. Two ctDNA samples were collected before and after crizotinib treatment. The different colors represent different gene mutation sites, as measured by NGS platform.. Abbreviations: NSCLC, non-small cell lung cancer; ctDNA, circulating tumor DNA; NGS, next-generation sequencing.
case_images: OTT-13-4183-g0001.jpg
case_images: PMC7234975_01_OTT-13-4183-g0001.jpg
case_images: F0001
case_images: The timeline of his diagnosis and treatment was shown in Figure 1A and the detailed description was as follows. The initial chest computed tomographic (CT) scan showed an irregular mass shadow with the size of 7x4 cm in the right middle lobe, accompanied by local atelectasis, mediastinal lymphadenopathy and right lower hilar lymph node enlargement of 4x4 cm (Figure 1B). The chest CT scan showed a reduced right lung lesion of 3x3 cm, the size of lower hilar lymph node was down to 2.5x2.5 cm and local atelectasis and pericardial effusion were alleviated (Figure 1B). The patient was given two cycles of chemotherapy (PP regimen + bevacizumab) but improvements were not observed after a thorough re-examination (Figure 1B). The breakpoint was inside intron 1 of HPCAL1 and intron 19 of ALK and the abundance of the fusion gene was 1.87% (Figure 1D, 2A and B). The efficacy evaluation was PR (Figure 1C). In April 2019, the re-examination CT scan revealed that the lesion at the right lung bronchus was almost disappeared, bilateral pleural effusion and pericardial effusion were nearly absorbed, but the tumor at the hilar lymph node was enlarged and the inflammation in the right lower lung was aggravated (Figure 1C). The cranial MRI results showed multiple brain metastases, with a maximum lesion of 0.7x0.7 cm (Figure 1C). A second NGS detection in ctDNA was performed and the HPCAL1-ALK fusion was identified again at the abundance rate of 0.36% (Figure 1D). The cranial MRI image showed that the brain metastases almost disappeared (Figure 1C).
case_images: Identification of the novel HPCAL1-ALK fusion.. Notes: (A) Structural illustration showed the HPCAL1-ALK fusion variant. (B) IGV image showed chimeric reads indicated HPCAL1-ALK fusion by NGS platform. (C) The representative FISH image showed split red-green or single red dots which indicating ALK fusion. Vysis ALK Break Apart Fish Probe Kit and Olympus Model BX51 Fluorescent Microscope were used for FISH detection. (D) The representative IHC staining image showed a strong protein expression, using ALK D5F3 (Ventana; 300X). Abbreviations: IGV, integrative genomics viewer; NGS, next-generation sequencing; FISH, fluorescence in situ hybridization; IHC, immunohistochemical.
case_images: OTT-13-4183-g0002.jpg
case_images: PMC7234975_01_OTT-13-4183-g0002.jpg
case_images: F0002
case_images: The breakpoint was inside intron 1 of HPCAL1 and intron 19 of ALK and the abundance of the fusion gene was 1.87% (Figure 1D, 2A and B). The HPCAL1-ALK fusion variant was then confirmed by fluorescence in situ hybridization (FISH) and immunohistochemical (IHC) in formalin fixed paraffin-embedded (FFPE) tissues (Figure 2C and D).