Prognostic and therapeutic significance of myeloma genetics and gene expression profiling.
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.
Stewart
A Keith
AK
Hematology-Oncology, Room 3-008, Mayo Clinic College of Medicine, Scottsdale, AZ 85259, USA. kstewart@uhnres.utoronto.ca
Fonseca
Rafael
R
D002869:Chromosome Aberrations; D002882:Chromosomes, Human, Pair 13; D002883:Chromosomes, Human, Pair 14; D003131:Combined Modality Therapy; D020732:Cytogenetic Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D011379:Prognosis; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis