Fig. 4: Reactivation of transcription by CIITA is sufficient to generate functional HLA-DRB1-ROS1 and CD74-ROS1 fusions.
From: Mechanistic patterns and clinical implications of oncogenic tyrosine kinase fusions in human cancers
a Experimental design to select osimertinib-resistant clones in CIITA-expressing PC-9 cells. b Circos plot showing the genome-wide distribution of ROS1 fusion partners identified in osimertinib-resistant cells obtained as described in (a). Arcs represent functional rearrangements joining ROS1 (exon 34, 35 or 36) to the indicated fusion partner. c, Schematic structural composition of HLA-DRB1-ROS1 H5del14;R34 fusion proteins. Protein domains are indicated by color and include: SS, signal sequence; TM, transmembrane domain; Kinase, ROS1 tyrosine kinase domain. d Detection of HLA-DRB1-ROS1 transcripts in CIITA-expressing PC-9 cells. e Experimental design to select osimertinib resistant clones driven by CD74-ROS1 fusions in both PC-9 cells and CIITA-expressing PC-9 cells. f Quantification of osimertinib-resistant clones in PC-9 and PC-9-CIITA cells. Data show means of five biological replicates, with error bars representing ±s.e.m; significance was determined by an unpaired, two-tailed Student’s t-test. g, h Detection of CD74-ROS1 fusion by genomic DNA PCR (g) and RT-PCR (h). Similar results were obtained from n = 2 independent experiments. i Detection of CD74-ROS1 transcripts in PC-9 and CIITA-expressing PC-9 cells. Similar results were obtained from n = 15 resistant clones. Source data are provided as a Source Data file.
