March 23, 2018

Kinase domain activation through gene rearrangement in multiple myeloma

Leukemia. 2018 Mar 23. doi: 10.1038/s41375-018-0108-y

Morgan GJ, He J, Tytarenko R, Patel P, Stephens OW, Zhong S, Deshpande S, Bauer M, Weinhold N, Schinke C, Rasche L, Bailey M, Ali S, Ross J, Miller VA, Stephens P, Thanendrarajan S, Zangari M, van Rhee F, Mughal T, Davies FE, Walker BA


Chromosomal rearrangements that result in oncogenic kinase activation are present in many solid and hematological malignancies, but none have been reported in multiple myeloma (MM). Here we analyzed 1421 samples from 958 myeloma patients using a targeted assay and detected fusion genes in 1.5% of patients. These fusion genes were in-frame and the majority of them contained kinase domains from either receptor tyrosine kinases (ALK, ROS1, NTRK3, and FGFR1) or cytoplasmic kinases (BRAF, MAP3K14, and MAPK14), which would result in the activation of MEK/ERK, NF-κB, or inflammatory signaling pathways. Fusion genes were present in smoldering MM, newly diagnosed MM, and relapse patient samples indicating they are…

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