Extended Data Fig. 4: Novel kinase mutations and fusions identified in patients with histiocytic neoplasms in this study.
From: Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms
(a) Protein diagrams of novel, somatic point mutations uncovered in kinases in histiocytoses in this study, as well as whether they have been previously described as somatic in cancer (noted by an asterisk, ‘*’) and/or functionally characterized (noted by pound sign, ‘#’).Of the 14 mutations illustrated, the RAF1 K106N5, MEK2 Y134H5, JAK3 V722I26, KIT V530I27, and CSF3R T64028 mutations have been shown to be activating previously. Also, four co-existed with other kinase alterations in the following combinations: CSF3R R583H mutation co-occurred with CSF3R T640I in a JXG patient, KIT R888W mutation co-occurred with MEK1 F53L in a histiocytic sarcoma patient, KIT V530I mutations co-occurred with a MEK1 V93I mutation in a JXG patient. (b) BRAF fusions, (c) NTRK1 fusions, (d) and ALK fusions identified. Hematoxylin and eosin (H&E) and anti-NTRK1 and anti-ALK immunohistochemical staining shown in TPM3-NTRK1-rearranged juvenile xanthogranuloma and KIF5B-ALK-rearranged Erdheim-Chester Disease tumor biopsies, respectively.
