Classifier for the molecular classification of multiple myeloma

Abstract

This disclosure is in the field of molecular diagnostics and relates to a method for classifying samples obtained from patients diagnosed with multiple myeloma into three newly defined clusters. The disclosure also relates to a method for determining the prognosis of an individual diagnosed with multiple myeloma as well as a method for the prediction of the response to treatment of an individual diagnosed with multiple myeloma. More in particular, the disclosure provides a method for determining the disease outcome or the prognosis of a patient diagnosed with multiple myeloma by classifying the patient into a high risk or a low risk category, based on a 92-gene classifier.

What is claimed is: 
     
         1 . A method for determining the prognosis of a subject diagnosed with multiple myeloma by classifying the patient into a high risk or a low risk category, the method comprising:
 determining the expression level in a sample from the subject for each of the following 92 genes: SLC30A7, AK2, SYF2, S100A6, NUF2, DARS2, ARPC5, DTL, ANGEL2, LBR, TARBP1, GGPS1, LTBP1. FAM49A, MCM6, ACVR2A, GRB14, ITGA6, DHRS9, STAT1, SPATS2L, BCS1L, SFMBT1, ARL8B, POLQ, MCM2, CCRL1, SEC62, GABRA4, PGM2, NCAPG, FGFR3, SEPT11, AIMP1, CENPE, IL7R, DHFR, SAR1B, PCDHB7, ATP6V0E1, MCM3, TUBB, MARCKS, SLC17A5, NCUBE1, SUN1/GET4, DNAJB9, RAB2A, TRAM1, ZNF252, HNRNPK, MRPL41, ZWINT, FANCF, EHBP1L1, C15orf85, PPP2R1B, ROBO3, C1S, ESPL1, ITM2B, ZBTB25, NPC2, ATPBD4, C15orf38, FANCI, SMG1, DYNLRB2, TMEM97, SPAG5, TOP2A, BIRC5, C18orf10, TSPAN16, RPS28, RPS11, NOP56, FTL, CDH22, DONSON, PFKL, ST13, DUX4, RPS4X, KIF4A, HMGN5, HMGB3, MAGEA6, the gene at chromosome 8p12 detectable with probe 208232_x_at, the gene at chromosome 11p14.1 detectable with probe 243018_at, and the gene at chromosome 11q24.3 detectable with probe 238780_s_at; and   classifying the subject into a high risk or a low risk category based upon the gene expression levels from the 92 genes.   
     
     
         2 . The method according to  claim 1 , wherein the sample comprises plasma cells. 
     
     
         3 . The method according to  claim 2 , wherein determining the gene expression level comprises:
 providing a probe set for the detection of each of the 92 genes;   contacting the probe set with a sample comprising mRNA from the subject; and   determining the expression level of each of the 92 genes.   
     
     
         4 . The method according to  claim 3 , wherein the gene expression analysis is performed on a gene chip. 
     
     
         5 . The method according to  claim 4 , wherein the method comprises
 contacting a gene chip comprising probes for the detection of the genes with a sample comprising mRNA from the subject;   determining the expression level of the genes;   normalizing the expression levels using mean/variance normalization to obtain a normalized expression value for each gene;   multiplying the normalized expression value for each gene with the beta value for each gene to obtain the calculated value for each gene; and   determining a score by summation of the calculated values of the genes,   wherein a score above a predetermined threshold indicates that the subject is to be classified in the high risk category and a score at or below the predetermined threshold indicates that the subject is to be classified in the low risk category.