Abstract
BackgroundMultiple myeloma is an incurable disease. Little is known about the genetic and molecular mechanisms governing the pathogenesis of multiple myeloma. The risk of multiple myeloma predispositions varies among different ethnicities. More than 50% of myeloma cases showed normal karyotypes with conventional cytogenetic analysis due to the low mitotic activity and content of plasma cells in the bone marrow. In the present study, high resolution array comparative genomic hybridization technique was used to identify copy number aberrations in 63 multiple myeloma patients of Malaysia.ResultsCopy number aberrations were identified in 100% of patients analyzed (n = 63). Common chromosomal gains were detected at regions 1q, 2q, 3p, 3q, 4q, 5q, 6q, 8q, 9q, 10q, 11q, 13q, 14q, 15q, 21q and Xq while common chromosomal losses were identified at regions 3q and 14q. There were a total of 25 and 5 genes localized within the regions of copy number gains and losses, respectively (>30% penetrance). The LYST, CLK1, ACSL1 and NFKBIA are genes localized within the copy number aberration regions and they represent novel information that has never been previously described in multiple myeloma patients.ConclusionsIn general, due to the differences in genetic background, dietary and lifestyle practices of Malaysian compared to the Caucasian population, these chromosomal alterations might be unique for Asian MM patients. Genes identified in this study could be potential molecular therapeutic targets for the treatment and management of patients with multiple myeloma.
Highlights
Information obtained in this study provides a better understanding on the chromosomal copy number changes in Asian compared to the Caucasian population
Copy number aberrations were found in 100% of MM patients The presence of copy number changes in 63 MM patients were analyzed by array CGH
To sum up, the development of malignant plasma cells is caused by the genetic defects within the tumor and the interaction between myeloma cells and the bone marrow micro-environment
Summary
Little is known about the genetic and molecular mechanisms governing the pathogenesis of multiple myeloma. High resolution array comparative genomic hybridization technique was used to identify copy number aberrations in 63 multiple myeloma patients of Malaysia. Multiple myeloma is an incurable disease and, little is known about the genetic and molecular mechanism governing its pathogenesis [3]. Various regions of chromosomal copy number aberrations have been described in MM including the deletions of 1p, 6q, 8p, 13q, 16q, 17p and 22q and gains of 1q, 6p, 9q, 11q, 12q, 15q, 17q, and 19q [7,8,9,10,11,12]. Short arm of chromosome 1 is commonly deleted, whereas the long arm tends to be amplified in MM [20]
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