Fig. 2: Molecular profiling of FGFR1 at clinical resistance, sensitivity of FGFR1 N546K to FGFR1 inhibitors, and longitudinal monitoring of the ZMYM2::FGFR1 fusion.
From: The FGFR1 N546K mutation confers resistance to pemigatinib in MLN-ZMYM2::FGFR1
A ZMYM2::FGFR1 fusion and FGFR1 mutation. Schematic representation of the breakpoints in ZMYM2 and FGFR1 involved in the fusion transcript. The FGFR1 exon 12 sequence (amino acids 538-554) is shown, highlighting the c.1638C>A point mutation (red) identified in DNA isolated from the progressive thoracic wall myeloid sarcoma. B Sensitivity of the FGFR1 N546K mutation to FGFR1 inhibitors. Cell viability of NCI-H1581 cells stably transduced with either FGFR1 wild-type or FGFR1 N546K mutant following treatment with multiple FGFR inhibitors. The mean of four independent biological replicates is depicted ± standard error of the mean. Statistical significance calculated by a two-sided Student’s t-test is indicated. C Longitudinal monitoring of ZMYM2::FGFR1 transcript levels. Droplet digital PCR (ddPCR) tracking of ZMYM2::FGFR1 transcript levels in bone marrow (BM) and peripheral blood (PB) over the disease course. BM bone marrow, cDNA complementary DNA, ddPCR droplet digital polymerase chain reaction, FGFR1 fibroblast growth factor receptor 1, PB peripheral blood, ZMYM2 Zinc Finger MYM-Type Containing 2.
