Genetic architecture of Multiple Myeloma and its prognostic implications - An updated review

Multiple myeloma (MM), a clonal B-cell neoplasia, is an incurable and heterogeneous disease where survival ranges from a few months to more than 10 years. The clinical heterogeneity of MM arises from multiple genomic events that result in tumour development and progression. Recurring genomic abnormalities including cytogenetic abnormalities, gene mutations and abnormal gene expression profiles in myeloma cells have a strong prognostic power. With the advancement in technologies and the development of novel drugs, the prognostic factors and treatment paradigms of MM have been fast evolving over the past few years. Following the introduction of new highthroughput cytogenomic technologies such as array comparative genome hybridisation (aCGH) or single nucleotide polymorphism array (SNP array) and molecular techniques such as gene expression profiling (GEP) and massively parallel genomic sequencing, the prediction of survival in MM no longer solely depends on conventional cytogenetics and interphase fluorescence in situ hybridisation (iFISH) analysis findings. These new technologies enable screening for all possible chromosomal aberrations and other genomic alterations, identifying each aberration on a case-bycase basis and discovering new aberrations that are relevant in unraveling the tumor cells' complex biology. This in turn allows a better understanding of the disease complexity and heterogeneity. The objective of this review on the genetic architecture of MM is to discuss the latest developments on the cytogenetic/cytogenomic-based risk classification of MM that are currently in use and their prognostic implications.