This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chng, W. J. Articles by Fonseca, R. Search for Related Content PubMed PubMed Citation Articles by Chng, W. J. Articles by Fonseca, R.

Molecular Dissection of Hyperdiploid Multiple Myeloma by Gene Expression Profiling

¹ Department of Hematology-Oncology, Mayo Clinic, Scottsdale, Arizona; ² Division of Hematology, Mayo Clinic, Rochester, Minnesota; ³ Translational Genomics Research Institute, Phoenix, Arizona; ⁴ Department of Computer Science and Engineering, Arizona State University, Tempe, Arizona; and ⁵ Millenium Pharmaceuticals, Inc., Cambridge, Massachusetts

Requests for reprints: Wee J. Chng, Division of Hematology-Oncology, Mayo Clinic, Johnson Research Building, 13400 East Shea Boulevard, Scottsdale, AZ 85260. Phone: 480-301-6363; Fax: 480-301-9162; E-mail: Chng.wee{at}mayo.edu.

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-B 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]

This article has been cited by other articles:

				O. Decaux, L. Lode, F. Magrangeas, C. Charbonnel, W. Gouraud, P. Jezequel, M. Attal, J.-L. Harousseau, P. Moreau, R. Bataille, et al. Prediction of Survival in Multiple Myeloma Based on Gene Expression Profiles Reveals Cell Cycle and Chromosomal Instability Signatures in High-Risk Patients and Hyperdiploid Signatures in Low-Risk Patients: A Study of the Intergroupe Francophone du Myelome J. Clin. Oncol., October 10, 2008; 26(29): 4798 - 4805. [Abstract] [Full Text] [PDF]