PMC5871789_01
a1-a3 Hematoxylin and eosin stained section of IMT. b Fluorescence in situ hybridization of post-crizotinib sample tissue, confirming rearrangement of ALK in 2p23: Isolated red signals (arrows) indicate loss of the 5' region of ALK. Orange fusion signals of the red 3' probe and the green 5' probe indicate normal ALK alleles. c Sanger sequencing of ALK of the initial tumor sample (C1) and the post-crizotinib sample (C2) identifying the ALK
G1269A resistance mutation. d Schematic illustration of the DCTN1-ALK fusion. Exons 20-29 of the ALK gene, which contain the tyrosine kinase domain, are fused with exons 1-26 of the DCTN1 gene. Both genes are located on chromosome 2p. The 5' region of ALK was apparently lost as indicated by the absence of the green FISH signal
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PMC5871789_01_41698_2017_4_Fig1_HTML.jpg
Fig1
Massively parallel (MPS) and hybrid-capture sequencing identified dynactin subunit 1 gene (DCTN1) as fusion partner and revealed the acquisition of an ALK G1269A mutation (confirmation by Sanger sequencing; Fig. 1).
Metabolic response evaluation and CRP levels. a Baseline 18FDG-PET/CT and follow-up scans showing metabolic response with decreasing uptake. b Non-linear chart of serum CRP levels (mg/L) (blue graph) and change of SUVmax in the single hottest lesion (red columns). Gray arrows: ceritinib treatment at daily doses indicated (mg); blue graph: CRP levels (mg/L); red columns: SUVmax of the hottest lesion
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PMC5871789_01_41698_2017_4_Fig2_HTML.jpg
Fig2
Baseline 18FDG-PET/CT scan showed local progression and the appearance of new thoracic lesions (sum of target lesions: 122 mm; SUVmax: 29.8; Fig. 2). SUVmax and a reduction of target lesions by 30% (86 mm; unconfirmed partial response; Fig. 2). Subsequently CRP levels rose and tumor related symptoms recurred.