Molecular Characterization of Human Multiple Myeloma Cell Lines by Genome-Wide Profiling.

Abstract 1793

Poster Board I-819

Multiple Myeloma (MM) is a malignancy depicted by clonal expansion of plasma cells in the bone marrow. There are two broad genetic subtypes of multiple myeloma as defined as hyperdiploid multiple myeloma (H-MM), characterized by trisomies of chromosomes 3, 5, 7, 9, 11, 15, 19, and 21, and nonhyperdiploid multiple myeloma (NH-MM) associated with primary translocations involving the immunoglobulin heavy chain (IgH). These two subtypes of multiple myeloma have two different molecular pathogenesis and characteristic changes of each have been already observed. In our study, we previously described the patterns of genetic lesions and molecular pathogenesis of 12 HMCLs with Affymetrix 500K Single Nucleotide Polymorphism-based mapping arrays, now we re-depict those patterns using the Illumina 1M array set and compare the two studies. These techniques allow the examination and identification of copy number changes, bi-allelic deletions and the identification of loss of heterozygosity (LOH) due to loss and uniparental disomy (UPD), as well as gene localization and identification. The 12 HMCLs utilized are characterized for their structural alterations and not by hyperdiploidy. In addition, so as to fulfill the selection criteria, a minimum of 3 cell lines must present the alterations cited below. Previously described gains were observed in 1q, 7q, 8, 11q, 18, 19, and 20q; but also found at 4q. The bi-allelic deletions were ascertained on 3p. Similarly, we identified the regions of mono-allelic deletions on 1, 2q, 6q, 8q, 9p, 11q, 12, 13q, 14q, 17p, and 20p. In addition, described regions of bi-allelic deletions were detected on 1p, 6q, 8p, 13q, 16q, and 22q, and furthermore located on 2q, 3, 4q, 9, 10q, 12p, and 20p. Finally, the UPD obtained were traced on 1q, 4q, 8q, 10q, and 22q. The use of the new platform has allowed us to re-identify, significantly increase in information above the original set and finely delimit the regions previously described. Taken together, the dysregulated genes from the myeloma genome indicate that the crucial pathways in myeloma include NF-kB, apoptosis, cell-cycle and critical intracellular signaling pathways including the JAK/STAT, Wnt signaling, RAS/RAF/MAPK and PI3k/AKT.