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

Francesco Maura (), David G. Coffey, Caleb K. Stein, Esteban Braggio, Bachisio Ziccheddu, Meaghen E. Sharik, Megan T. Du, Yuliza Tafoya Alvarado, Chang-Xin Shi, Yuan Xiao Zhu, Erin W. Meermeier, Gareth J. Morgan, Ola Landgren, P. Leif Bergsagel and Marta Chesi ()
Additional contact information
Francesco Maura: University of Miami
David G. Coffey: University of Miami
Caleb K. Stein: Mayo Clinic
Esteban Braggio: Mayo Clinic
Bachisio Ziccheddu: University of Miami
Meaghen E. Sharik: Mayo Clinic
Megan T. Du: Mayo Clinic
Yuliza Tafoya Alvarado: Mayo Clinic
Chang-Xin Shi: Mayo Clinic
Yuan Xiao Zhu: Mayo Clinic
Erin W. Meermeier: Mayo Clinic
Gareth J. Morgan: NYU Langone, Perlmutter Cancer Center
Ola Landgren: University of Miami
P. Leif Bergsagel: Mayo Clinic
Marta Chesi: Mayo Clinic

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract 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 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 and immortalized murine MM tumors.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-48091-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48091-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-48091-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().