Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling

Wee J. Chng, Shaji Kumar, Scott VanWier, Greg Ahmann, Tammy Price-Troska, Kim Henderson, Tae Hoon Chung, Seungchan Kim, George Mulligan, Barbara Bryant, John Carpten, Morie Gertz, S. Vincent Rajkumar, Martha Lacy, Angela Dispenzieri, Robert Kyle, Philip Greipp, P. Leif Bergsagel, Rafael Fonseca

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177 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)2982-2989
Number of pages8
JournalCancer research
Volume67
Issue number7
DOIs
StatePublished - Apr 1 2007

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chng, W. J., Kumar, S., VanWier, S., Ahmann, G., Price-Troska, T., Henderson, K., Chung, T. H., Kim, S., Mulligan, G., Bryant, B., Carpten, J., Gertz, M., Rajkumar, S. V., Lacy, M., Dispenzieri, A., Kyle, R., Greipp, P., Bergsagel, P. L., & Fonseca, R. (2007). Molecular dissection of hyperdiploid multiple myeloma by gene expression profiling. Cancer research, 67(7), 2982-2989. https://doi.org/10.1158/0008-5472.CAN-06-4046