Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling
| Autor: | Seungchan Kim, Shaji Kumar, Rafael Fonseca, Martha Q. Lacy, Morie A. Gertz, Greg J. Ahmann, Tae-Hoon Chung, P. Leif Bergsagel, Wee Joo Chng, George Mulligan, Philip R. Greipp, Scott VanWier, Tammy Price-Troska, Angela Dispenzieri, Robert A. Kyle, John D. Carpten, S. Vincent Rajkumar, Kim Henderson, Barbara M. Bryant |
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| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
Antineoplastic Agents Trisomy Biology Dexamethasone Plasma Cell Labeling Index Bortezomib Cohort Studies Immunopathology medicine Humans Gene Multiple myeloma In Situ Hybridization Fluorescence Genetics Gene Expression Profiling A protein medicine.disease Prognosis Boronic Acids Diploidy Gene expression profiling Dissection Oncology Multigene Family Protein Biosynthesis Pyrazines Cancer research Cancer/testis antigens Multiple Myeloma |
| Zdroj: | Cancer research. 67(7) |
| ISSN: | 0008-5472 |
| Popis: | 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-κB 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. [Cancer Res 2007;67(7):2982–9] |
| Databáze: | OpenAIRE |
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