Systematic name M15555
Brief description Protein biosynthesis, transport or catabolism genes up-regulated in hyperploid multiple myeloma (MM) compared to the non-hyperploid MM samples.
Full description or abstract Hyperdiploid multiple myeloma (H-MM) is the most common form of myeloma. In this gene expression profiling study, we show that H-MM is defined by a protein biosynthesis signature that is primarily driven by a gene dosage mechanism as a result of trisomic chromosomes. Within H-MM, four independently validated patient clusters overexpressing nonoverlapping sets of genes that form cognate pathways/networks that have potential biological importance in multiple myeloma were identified. One prominent cluster, cluster 1, is characterized by high expression of cancer testis antigen and proliferation-associated genes. Tumors from these patients were more proliferative than tumors in other clusters (median plasma cell labeling index, 3.8; P < 0.05). Another cluster, cluster 3, is characterized by genes involved in tumor necrosis factor/nuclear factor-kappaB signaling and antiapoptosis. These patients have better response to bortezomib as compared with patients within other clusters (70% versus 29%; P = 0.02). Furthermore, for a group of patients generally thought to have better prognosis, a cluster of patients with short survival (cluster 1; median survival, 27 months) could be identified. This analysis illustrates the heterogeneity within H-MM and the importance of defining specific cytogenetic prognostic factors. Furthermore, the signatures that defined these clusters may provide a basis for tailoring treatment to individual patients.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17409404   Authors: Chng WJ,Kumar S,Vanwier S,Ahmann G,Price-Troska T,Henderson K,Chung TH,Kim S,Mulligan G,Bryant B,Carpten J,Gertz M,Rajkumar SV,Lacy M,Dispenzieri A,Kyle R,Greipp P,Bergsagel PL,Fonseca R
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