Diagnosis, Prognosis and Identification of Potential Therapeutic Targets of Multiple Myeloma Based on Gene Expression Profiling

摘要

Gene expression profiling is a powerful tool that has varied utility. It enables classification of multiple myeloma into subtypes and identifying genes directly involved in disease pathogensis and clinical manifestation. The present invention used gene expression profiling in large uniformly treated population of patients with myeloma to identify genes associated with poor prognosis. It also demonstrated that over-expression of CKS1B gene, mainly due to gene amplification that was determined by Fluorescent in-situ hybridization to impart a poor prognosis in multiple myleoma. It is further contemplated that therapeutic strategies that directly target CKS1B or related pathways may represent novel, and more specific means of treating high risk myeloma and may prevent its secondary evolution.

主权项

1. A method of determining the prognosis of a human subject with monoclonal gammopathy of undetermined significance (MGUS), comprising the steps of:
determining gene expression levels of GNG10, PNPLA4, KIAA1754, AHCYL1, MCLC, EVI5, AD-020, PARG1, CTBS, FUCA1, RFP2, FLJ20489, LTBP1, TRIP13, AIM2, SELI, SLC19A1, LARS2, OPN3, ASPM, CCT2, UBE21, STK6, FLJ13052, FLJ12525, BIRC5, CKS1B, CKAP1, MGC57827, DKFZp7790175, PFN1, ILF3, IFI16, TBRG4, PAPD1, EIF2C2, MGC4308, ENOL, DSG2, EXOSC4, TAGLN2, RUVBL1, ALDOA, CPSF3, MGC15606, LGALS1, RAD18, SNX5, PSMD4, RAN, KIF14, CBX3, TMPO, DKFZP586L0724, WED, ROBO1, TCOF1, YWHAZ, and MPHOSPH1 in plasma cells isolated from the human patient, wherein the gene expression levels are determined using an artificially and detectably labeled sample from the plasma cells, further wherein the sample is an isolated nucleic acid sample or an isolated protein sample; and comparing the expression levels to one or more suitable controls and assigning the patient a prognosis on the basis of the comparison, wherein:
reduced expression of GNG10, PNPLA4, KIAA1754, AHCYL1, MCLC, EVI5, AD-020, PARG1, CTBS, FUCA1, RFP2, FLJ20489, or LTBP1, relative to a control with a favorable prognosis, is associated with a poor prognosis; andoverexpression of TRIP13, AIM2, SELL SLC19A1, LARS2, OPN3, ASPM, CCT2, UBE21, STK6, FLJ13052, FLJ12525, BIRC5, CKS1B, CKAP1, MGC57827, DKFZp7790175, PFN1, ILF3, IFI16, TBRG4, PAPD1, EIF2C2, MGC4308, ENOL, DSG2, EXOSC4, TAGLN2, RUVBL1, ALDOA, CPSF3, MGC15606, LGALS1, RAD18, SNX5, PSMD4, RAN, KIF14, CBX3, TMPO, DKFZP586L0724, WEE1, ROBO1, TCOF1, YWHAZ, or MPHOSPH1, relative to a control with a favorable prognosis, is associated with a poor prognosis.