High Resolution Characterization of Multiple Myeloma using Array CGH
High Resolution Characterization of Multiple Myeloma using Array CGH
A review of Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations
Note: This is a review of the published article listed below. All information, quotes, figures, methods, and findings mentioned in this review are from that article, and are the property of its authors and/or the publication in which the article originally appeared.
Multiple myeloma (MM) is an incurable malignant plasma cell neoplasia in the bone marrow, currently characterized as either hyperdiploid, containing multiple trisomies, or non-hyperdiploid, containing a number of translocations and other structural rearrangements. In this pioneering research, Largo and colleagues (2007) used Agilent’s Human Genome CGH 44k microarrays to analyze 26 primary MM samples after the enrichment of CD138-positive plasma cells, for the first time. Using the Agilent aCGH platform, the group was able to “identify copy number changes in 100% of the primary MM samples. [They segregated] different MM subgroups based on their genomic profiles to identify homozygous deletions and amplifications of great genetic relevance in MM.” These results demonstrate for the first time that extreme genomic aberrations, such as high level amplifications and homozygous deletions, are frequent events in MM. The researchers believe that these data warrant further investigation to gain a deeper insight into the role of genomic instability in MM and its potential use for therapeutic purposes.
Figure 1. Unsupervised clustering results, ideograms showing array CGH profiles and SKY images.
A. Unsupervised clustering revealing the molecular heterogeneity in primary MM samples. Unsupervised clustering was carried out with 68 SORI identified. The analysis segregated the hyperdiploid cases from the non-hyperdiploid ones. The H-MM group could be divided in two subgroups. Statistically significant SORI that separated H-MM and NH-MM are highlighted with a blue key, and chromosome 13 deletion and 1q duplication are marked with gray arrows. B. Red and blue lines depict the 500 Kb moving average CGH ratio. Bars on the left indicate losses and bars on the right gains (
-score threshold of 2). Left ideogram. Chromosomes X, 13 and 21 array CGH plots and SKY picture of case #20. The sample was from a male, the control DNA was a pool of female DNA. Xq duplication is depicted as a normal pattern after a loss. Chromosome 21 trisomy and chromosome 13 homozygous deletions are also shown. SKY assays confirmed the array CGH results and revealed that the Xq21 duplicated fragment and remaining chromosome 13 were involved in different translocations. Right ideogram. Array CGH profiles of chromosome X and 14 showing Xq21 duplication and chromosome 14 breakpoint in L363. SKY analysis showed that the duplicated fragment was involved in a translocation with chromosome 14.
Title: Multiple myeloma primary cells show a highly rearranged unbalanced genome with amplifications and homozygous deletions irrespective of the presence of immunoglobulin-related chromosome translocations.
Authors: Largo C, Saéz B, Alvarez S, Suela J, Ferreira B, Blesa D, Prosper F, Calasanz MJ, Cigudosa JC.
Journal: Haematologica. 2007 Jun;92(6):795-802
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