Fusion of Platelet Derived Growth Factor Receptor Alpha (PDGFRA) With Ubiquitin Specific Peptidase 8 (USP8) in a Calcified Chondroid Mesenchymal Neoplasm Harboring t(4;15)(q12;q21) as a Sole Aberration

IOANNIS PANAGOPOULOS; KRISTIN ANDERSEN; LUDMILA GORUNOVA; INGVILD LOBMAIER

doi:10.21873/cgp.20444

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Figure 1.
Microscopic examination of the calcified chondroid mesenchymal neoplasm. Hematoxylin and eosin (H&E) stained section showing polygonal to epithelioid cells in a chondrohyaline matrix with areas of fine and coarse calcification. (A) Magnification ×100. (B) Magnification ×200.
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Figure 2.
Genetic examination of the calcified chondroid mesenchymal neoplasm. (A) Partial karyogram showing the der(4)t(4;15)(q12;q21) and der(15)t(4;15)(q12;q21) together with the corresponding normal chromosome homologs. Breakpoint positions are indicated by arrows. (B) Gel electrophoresis showing the amplified ABL1 (lane 1), PDGFRA::USP8 (lane 2) and USP8::PDGFRA (lane 3) cDNA fragments using the primer combinations ABL1-91F1/ABL1-404R1, PDGFRA-3033F1/USP8-1027R1, and USP8-616F1/PDGFRA-3443R1, respectively. M: GeneRuler 1kb Plus DNA ladder (Thermo Fisher Scientific). (C) Partial sequence chromatogram showing the junction position in the PDGFRA::USP8 cDNA amplified fragment. (D) Partial sequence chromatogram showing the junction position in the USP8::PDGFRA cDNA amplified fragment. The exon numbers are based on the sequences with accession numbers NM_006206.6 for PDGFRA and NM_005154.5 for USP8. (E). Illustration showing the coding protein PDGFRA. SP: Signal peptide; IG1: Ig_3 immunoglobulin domain; IG2: immunoglobulin-like domain of platelet-derived growth factor receptors (PDGFR), alpha and beta, member of the I-set of IgSF domains; IG3: fourth immunoglobulin-like domain of PDGFR; TMR: transmembrane region; PTK-CD: catalytic domain of the protein tyrosine kinase. (F) Illustration showing the coding protein USP8. USP8-dimer: USP8 dimerization domain; Rhodanese: Rhodanese-like domain; tolA_full: TolA protein; UCH: ubiquitin carboxyl-terminal hydrolase; FP1: fusionpoint reported by Fisher et al. (2) in calcified mesenchymal neoplasm with PDGFRA::USP8; FP2: fusionpoint reported in the present study in a calcified mesenchymal neoplasm with PDGFRA::USP8; FP3: breakpoint reported in B-cell lineage acute lymphoblastic leukemia carrying KMT2A::USP8 chimera which was generated by chromosomal translocation t(11;15)(q23;q21) (50). The parts of the PDGFRA and USP proteins in yellow compose the chimeric PDGFRA::USP8 protein while the parts in cyan compose the chimeric USP8::PDGFRA protein.
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Figure 3.
Illustration showing the cell membrane location of the chimeric PDGFRA::USP8 protein. The illustration is based on the reference sequences NM_006206.6/NP_006197.1 for PDGFRA and NM_005154.5/NP_005145.3 for USP8. SP: Signal peptide; IG1: Ig_3 immunoglobulin domain; IG2: immunoglobulin-like domain of platelet-derived growth factor receptors (PDGFR), alpha and beta, member of the I-set of IgSF domains; IG3: fourth immunoglobulin-like domain of PDGFR; TMR: transmembrane region; Rhod: Rhodanese-like domain; tolA_full: TolA protein. Illustration was made with the Protter program (20).