A GENE EXPRESSION PROFILING BASED IDENTIFICATION OF GENOMIC SIGNATURES OF MULTIPLE MYELOMA AND USES THEREOF

摘要

Monoclonal gammopathy of undetermined significance can progress to multiple myeloma. Applying significance analysis of microarrays, 52 genes, involved in important pathways related to cancer, were differentially expressed between plasma cells from healthy subjects and patients with stringently defined monoclonal gammopathy of undetermined significance /smoldering multiple myeloma and symptomatic multiple myeloma. Unsupervised hierarchical clustering of 351 multiple myeloma and 44 cases of monoclonal gammopathy of undetermined significance and 16 cases of multiple myeloma with a monoclonal gammopathy of undetermined significance history, created two major cluster branches, one containing 82% of the monoclonal gammopathy of undetermined significance cases and 28% of the multiple myeloma, termed monoclonal gammopathy of undetermined significance-like multiple myeloma. Using the same clustering approach on an independent cohort of 213 cases of multiple myeloma revealed 27% with monoclonal gammopathy of undetermined significance-like multiple myeloma which, despite a lower incidence of complete remission, was associated with low-risk clinical and molecular features and superior survival. The monoclonal gammopathy of undetermined significance-like multiple myeloma signature was also seen in patients surviving more than 10 years after autotransplant.