Homozygous Deletions Can Be Used to Define a Cell Death Specific Gene Expression Signature Able to Predict Outcome in Myeloma

Defining biologically relevant prognostic indices in myeloma is a challenge. The International Staging System (ISS) is important but based on simple clinical data. Cytogenetics, in particular switch translocations and 17p-, are more important biologically, being based on underlying genetic changes. However, these changes do not capture all of the important biological data and so signatures based on global expression analysis have been developed to address these shortcomings. Most signatures to date have been based on expression features correlated with outcome rather than using structural genetic change to define biologically relevant expression features and, as such, although predictive, they may be acting as “bystander” markers rather than being pathologically important themselves. We have used homozygous deletions (HD) to define relevant genes and gene signatures predictive of outcome in a large homogeneously treated set of myeloma patients.