Nature communications, 2024-05, Vol.15 (1), p.3844-15, Article 3844
2024
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- Autor(en) / Beteiligte
- Titel
- The genomic landscape of VkMYC myeloma highlights shared pathways of transformation between mice and humans
- Ist Teil von
- Nature communications, 2024-05, Vol.15 (1), p.3844-15, Article 3844
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2024
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-024-48091-wTitel-ID: cdi_doaj_primary_oai_doaj_org_article_0fb36d4f85d4436b947de3da11cd1f2d
- Format
- –
- Schlagworte
- Alleles, Animal models, Animals, Apolipoprotein B, Cell Transformation, Neoplastic - genetics, Copy number, DNA Copy Number Variations - genetics, Genetic engineering, Genetic transformation, Genomics, Genomics - methods, Germinal centers, Heterogeneity, Humans, Insertional mutagenesis, Mice, Mice, Transgenic, Multiple myeloma, Multiple Myeloma - genetics, Multiple Myeloma - pathology, Mutagenesis, Mutagenesis, Insertional, Mutation, Myc protein, Neoplasms, NF-kappa B - genetics, NF-kappa B - metabolism, NF-κB protein, Polypeptides, Proto-Oncogene Proteins c-myc - genetics, Proto-Oncogene Proteins c-myc - metabolism, RNA editing, Signal Transduction - genetics, Translocation, Translocation, Genetic, Tumors