The genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans

The genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans

Blog Article

Abstract Multiple myeloma (MM) is a heterogeneous disease characterized by frequent MYC translocations.Sporadic MYC activation in the germinal center of genetically engineered pentair hose Vk*MYC mice is sufficient to induce plasma cell tumors in which a variety of secondary mutations are spontaneously acquired and selected over time.Analysis of 119 Vk*MYC myeloma reveals recurrent copy number alterations, structural variations, chromothripsis, driver mutations, apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) mutational activity, and a progressive decrease in immunoglobulin transcription that inversely correlates with proliferation.Moreover, we identify frequent insertional mutagenesis by endogenous retro-elements as a murine specific mechanism to activate NF-kB and IL6 signaling pathways shared with human MM.Despite the increased genomic complexity associated with progression, advanced tumors remain dependent on MYC.

In summary, here we credential the Vk*MYC mouse as a unique resource to explore MM genomic evolution and describe a fully annotated collection of diverse animed aniflex complete and immortalized murine MM tumors.