biostudies-literatureMaura FU.S. Department of Health & Human Services | NIH | National Cancer InstituteNCI NIH HHS3844https://www.ebi.ac.uk/biostudies/studies/S-EPMC11076575biostudies-literatureUnknown15(1)Multiple myeloma (MM) is a heterogeneous disease characterized by frequent MYC translocations. Sporadic MYC activation in the germinal center of genetically engineered 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 pathwayNature communicationsThe genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans.PMC11076575R01 CA234181CA186781U01 CA271410U54 CA224018P30 CA240139RO1CA234181P50 CA186781U54CA224018R01 CA272426Du MTZiccheddu BLandgren OTafoya Alvarado YShi CXMorgan GJStein CKSharik MEBraggio EZhu YXMeermeier EWMaura FChesi MCoffey DGBergsagel PLfalseThe genomic landscape of Vk*MYC myeloma highlights shared pathways of transformation between mice and humans.Multiple myeloma (MM) is a heterogeneous disease characterized by frequent MYC translocations. Sporadic MYC activation in the germinal center of genetically engineered 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 pathway2024-01-01T00:00:00Z2024 May2026-06-03T04:22:49.98Z2026-04-24T03:10:02.059ZS-EPMC110765753871469010.1038/s41467-024-48091-w