Increasing genomic discovery in newly diagnosed multiple myeloma: defining disease biology and its correlation to risk

Our understanding of MM genomics has expanded rapidly in the past 5–10 years as a consequence of cytogenetic analyses obtained in routine clinical practice as well as the ability to perform whole-exome/genome sequencing and gene expression profiling on large patient data sets. This knowledge has offered new insights into disease biology and is increasingly defining high-risk genomic patterns. In this manuscript, we present a thorough review of our current knowledge of MM genomics. The epidemiology and biology of chromosomal abnormalities including both copy number abnormalities and chromosomal translocation are described in full with a focus on those most clinically impactful such as 1q amplification and del(17p) as well as certain chromosome 14 translocations. A review of our ever-expanding knowledge of genetic mutations derived from recent whole-genome/exome data sets is then reviewed including those that drive disease pathogenesis from precursor states as well as those that may impact clinical outcomes. We then transition and attempt to elucidate how both chromosomal abnormalities and gene mutations are evolving our understanding of disease risk. We conclude by offering our perspectives moving forward as to how we might apply whole-genome/exome-level data in addition to routine cytogenetic analyses to improve patient outcomes as well as further knowledge gaps that must be addressed.