Integrating cytogenetics and gene expression profiling in the molecular analysis of multiple myeloma.
Multiple Myeloma (MM), is a currently incurable malignancy of a terminally differentiated antibody secreting plasma cell (PC) that can be controlled with high dose therapy and stem cell support. Conventional cytogenetic analysis has revealed a genomic instability that sets MM apart from the other blood cell cancers. In spite of this "genomic chaos" recurrent structural rearrangements and ploidy changes have aided the identification of important molecular mechanisms of disease etiology and that have also proved to be useful clinical landmarks. Yet, abnormal cytogenetics, present in only 30% of cases, combined with other clinical parameters, only account for 20% of the variability in clinical outcome, which can range from 2 months to > 10 years. Thus, the genomic chaos may mask a unifying chromosome abnormality, e.g. Philadelphia chromosome in CML, or may indicate that MM is a broad descriptor of constellation of many distinct clinical and molecular entities. The advent of microarray profiling of global gene expression patterns is providing evidence that both of these possibilities may be true. We will discuss how the integration of conventional and molecular cytogenetics with gene expression profiling has confirmed past observations and, yet fundamentally changed the way we view the disease.
Shaughnessy
John D
JD
Donna D. and Donald M Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, USA.
Barlogie
Bart
B
D002869:Chromosome Aberrations; D020732:Cytogenetic Analysis; D020869:Gene Expression Profiling; D018816:Genes, cdc; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies