Keywords
genomic instability
mutational signatures
epigenetics
How to Cite
Abstract
Genomic instability (GI) is a characteristic present in most types of cancer, defined as an increased genome trend to acquired different types of changes. Multiple myeloma (MM) is characterized by an important genetic heterogeneity manifested by numerous recurrent numerical and structural cytogenetic alterations, observed at diagnosis or acquired during disease evolution, supporting an important GI in this pathology. There are different forms of GI: chromosome instability (CIN), microsatellite instability (MSI) and nucleotide instability (NI). CIN is the most common form in human cancer. It is characterized by an accelerated rate of chromosome alterations during cellular divisions. There are different mechanisms related to CIN development, among them: DNA breakpoints at 1q12 associated to jumping translocations, chromothripsis, chromoplexy and template insertions. In addition, telomere shortening and replication asynchrony must be considered. On the contrary, there is few information about MSI in MM. In reference to NI, it is characterized by base substitutions and small insertions/ deletion (indels) that involve both the coding and non-coding genome, originating different mutational signatures that can affect distinct signaling pathways. The most relevant are: cytosine deaminases, APOBEC, AID aberrant activity and kataegis. They are associated to disease progression and resistance to treatment. Finally, it is important to point out the epigenetic alterations: DNA methylation, histone modifications and non-coding RNA expression, with an important role in neoplastic development. The study of GI mechanisms in MM will permit to deepen into the knowledge of the biologic characteristics of this pathology, making a contribution to the generation of novel therapies for these patients.
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