A Comprehensive Analysis Of Multiple Myeloma Genes Using Advanced Bioinformatics Tools

摘要

Multiple myeloma is a monoclonal B-cell malignancy which originates in lymph node germinal centers but locates and expands in bone marrow. Multiple Myeloma (MM) occurs when plasma cells grow excessively and interfere with the production of red blood cells, white blood cells, and the platelets. Genetic abnormalities in multiple myeloma have been a subject of interest to researchers, as an understanding of the complex karyotypes can be of great value in treatment of MM.The aim of our study is to provide a comprehensive analysis of MM genes for understanding the cytogenetics of the disease. The present investigation is based upon the identification of over 35 important multiple myeloma genes located on different chromosomes.Various aspects of these genes were studied using different in-silico tools. An attempt was made to study the domains and patterns exhibited by the proteins and correlate them to the landmark events in the formation of multiple myelomas. A close scrutiny of the nucleotide sequences of these genes was conducted for identifying any internal repeats within the sequence and their possible significance as biomarkers. Introduction Multiple myeloma is a malignancy of the immunoglobulin-producing plasma cells. Excessive plasma cells form tumors called myelomas. Though it is a hematological malignancy like leukemia, the myeloma cells rarely enter the blood stream and instead accumulate in bone marrow. As the tumors grow in the bone marrow, they cause a disruption of normal bone marrow function, giving rise to anemia. Other complications of multiple myeloma include increased susceptibility to infection, renal failure and bone fractures. High levels of calcium in the blood are seen in about a quarter of myeloma patients as a consequence of the increased bone destruction releasing calcium into the bloodstream.Cytogenetic aspects of Multiple myeloma have attracted the attention of researchers, as the karyotypes in MM are typically complex, in contrast to other hematologic malignancies. The genetic imbalances in multiple myeloma have been defined at molecular level and have shown that genomic changes may affect almost all chromosomes, as shown by extensive fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) 9. Several recurring chromosomal abnormalities have been identified including structural rearrangements (e.g., translocations of 14q32), trisomies (e.g., chromosome 15), and monosomies (e.g., chromosome 13)8. The frequency and extent of karyotypic abnormalities correlates with the disease stage, duration, and response to treatment.13.An analysis of the genes and the encoded proteins associated with multiple myeloma would be a necessary prerequisite towards a better understanding of the disease for an early diagnosis and more effective methods of treatment. The present study was taken up as a preliminary step and an attempt was made to analyze some important genes of MM.Besides collecting protein and nucleotide sequence data from large public Databases, an attempt was made to use most advanced bioinformatics tools to perform sequence retrieval, phylogenetic analysis, domain and pattern recognition, protein-to-protein interactions, micro satellite detection and repeat analysis etc. Methodology After a survey of the available literature, over 35 important myeloma genes were identified for investigation.A brief list of the major Databases and Bioinformatics tools employed during the study is given below.Databases: GenBank, GENECARDS Swiss-Prot, HUGO.