Gene Set: BOYLAN_MULTIPLE_MYELOMA_PCA1_UP

Standard name BOYLAN_MULTIPLE_MYELOMA_PCA1_UP
Systematic name M9399
Brief description Top up-regulated genes from principal component 1 (PCA1) which captures variation between normal plasma cells and tumors arising from aberrant expression of BCL2L1 and MYC [GeneID=598;4609].
Full description or abstract Multiple myeloma is an incurable plasma cell malignancy for which existing animal models are limited. We have previously shown that the targeted expression of the transgenes c-Myc and Bcl-X(L) in murine plasma cells produces malignancy that displays features of human myeloma, such as localization of tumor cells to the bone marrow and lytic bone lesions. We have isolated and characterized in vitro cultures and adoptive transfers of tumors from Bcl-xl/Myc transgenic mice. Tumors have a plasmablastic morphology and variable expression of CD138, CD45, CD38, and CD19. Spectral karyotyping analysis of metaphase chromosomes from primary tumor cell cultures shows that the Bcl-xl/Myc tumors contain a variety of chromosomal abnormalities, including trisomies, translocations, and deletions. The most frequently aberrant chromosomes are 12 and 16. Three sites for recurring translocations were also identified on chromosomes 4D, 12F, and 16C. Gene expression profiling was used to identify differences in gene expression between tumor cells and normal plasma cells (NPC) and to cluster the tumors into two groups (tumor groups C and D), with distinct gene expression profiles. Four hundred and ninety-five genes were significantly different between both tumor groups and NPCs, whereas 124 genes were uniquely different from NPCs in tumor group C and 204 genes were uniquely different from NPCs in tumor group D. Similar to human myeloma, the cyclin D genes are differentially dysregulated in the mouse tumor groups. These data suggest the Bcl-xl/Myc tumors are similar to a subset of plasmablastic human myelomas and provide insight into the specific genes and pathways underlying the human disease.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17483317   Authors: Boylan KL,Gosse MA,Staggs SE,Janz S,Grindle S,Kansas GS,Van Ness BG
Exact source Table 3S: Eigengene 1 Score > 0
Related gene sets (show 13 additional gene sets from the source publication)

(show 10 gene sets from the same authors)
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform Mouse430_2
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.0: First introduced

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