GENE EXPRESSION PROFILING BASED IDENTIFICATION OF GENOMIC SIGNATURE OF HIGH-RISK MULTIPLE MYELOMA AND USES THEREOF

摘要

The present invention discloses a method of applying novel bioinformatics and computational methodologies to data generated by high-resolution genome-wide comparative genomic hybridization and gene expression profiling on CD138-sorted plasma cells from a cohort of 92 newly diagnosed multiple myeloma patients treated with high dose chemotherapy and stem cell rescue. The results revealed that gains the q arm and loss of the p arm of chromosome 1 were highly correlated with altered expression of resident genes in this chromosome, with these changes strongly correlated with 1 ) risk of death from disease progression, 2) a gene expression based proliferation index, and 3) a recently described gene expression-based high-risk index. Importantly, a strong correlation was found between copy number gains of 8q24, and increased expression of Argonate 2 (AG02) a gene coding for a master regulator of microRNA expression and maturation, also being significantly correlated with outcome. These novel findings significantly improve the understanding of the genomic structure of multiple myeloma and its relationship to clinical outcome.