Human Gene Set: ZHAN_MULTIPLE_MYELOMA_PR_DN


Standard name ZHAN_MULTIPLE_MYELOMA_PR_DN
Systematic name M10412
Brief description Top 50 down-regulated genes in cluster PR of multiple myeloma samples characterized by increased expression of proliferation and cell cycle genes.
Full description or abstract To better define the molecular basis of multiple myeloma (MM), we performed unsupervised hierarchic clustering of mRNA expression profiles in CD138-enriched plasma cells from 414 newly diagnosed patients who went on to receive high-dose therapy and tandem stem cell transplants. Seven disease subtypes were validated that were strongly influenced by known genetic lesions, such as c-MAF- and MAFB-, CCND1- and CCND3-, and MMSET-activating translocations and hyperdiploidy. Indicative of the deregulation of common pathways by gene orthologs, common gene signatures were observed in cases with c-MAF and MAFB activation and CCND1 and CCND3 activation, the latter consisting of 2 subgroups, one characterized by expression of the early B-cell markers CD20 and PAX5. A low incidence of focal bone disease distinguished one and increased expression of proliferation-associated genes of another novel subgroup. Comprising varying fractions of each of the other 6 subgroups, the proliferation subgroup dominated at relapse, suggesting that this signature is linked to disease progression. Proliferation and MMSET-spike groups were characterized by significant overexpression of genes mapping to chromosome 1q, and both exhibited a poor prognosis relative to the other groups. A subset of cases with a predominating myeloid gene expression signature, excluded from the profiling analyses, had more favorable baseline characteristics and superior prognosis to those lacking this signature.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16728703   Authors: Zhan F,Huang Y,Colla S,Stewart JP,Hanamura I,Gupta S,Epstein J,Yaccoby S,Sawyer J,Burington B,Anaissie E,Hollmig K,Pineda-Roman M,Tricot G,van Rhee F,Walker R,Zangari M,Crowley J,Barlogie B,Shaughnessy JD Jr
Exact source Table 3S: Subgroup = PR
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 AFFY_HG_U133
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Version history 3.0: First introduced

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