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Prognostic and Therapeutic Significance of Myeloma Genetics and Gene Expression Profiling

A. Keith Stewart, Rafael Fonseca

From the Department of Medical Oncology, Princess Margaret Hospital, University Health Network; Ontario Cancer Institute, University Health Network; McLaughlin Center for Molecular Medicine, University of Toronto, Toronto, Ontario, Canada; and the Mayo Clinic College of Medicine, Scottsdale, AZ

Address reprint requests to A. Keith Stewart, MD, Hematology-Oncology, Room 3-008, Mayo Clinic College of Medicine, Scottsdale, AZ 85259; e-mail: kstewart{at}uhnres.utoronto.ca.

Molecular diagnostic tools and novel therapeutics now offer the potential for accurate prognostic and personalized treatment road maps for patients with multiple myeloma (MM). We will review the evidence and provide specific recommendations for routine clinical molecular genetic testing and use of such information to guide therapeutic decision making. In particular, the negative prognostic impact of specific IgH translocations such as the t(4;14), t(14;16), chromosome 13 deletion by conventional cytogenetics and loss of 17p13 by interphase fluorescence in situ hybridization are now established. Preliminary gene expression profiling studies have also demonstrated that individual genes (CSK1-B) or groups of genes can define prognosis with greater accuracy than conventional genetic markers and can provide pharmacogenomic and biologic insight into the pathophysiology, therapeutics, and future targets of myeloma. Importantly, we recommend that all clinical trials now adopt routine genetic testing and risk stratification.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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