Methods for identifying, diagnosing, and predicting survival of lymphomas

Abstract

Gene expression data provides a basis for more accurate identification and diagnosis of lymphoproliferative disorders. In addition, gene expression data can be used to develop more accurate predictors of survival. The present invention discloses methods for identifying, diagnosing, and predicting survival in a lymphoma or lymphoproliferative disorder on the basis of gene expression patterns. The invention discloses a novel microarray, the Lymph Dx microarray, for obtaining gene expression data from a lymphoma sample. The invention also discloses a variety of methods for utilizing lymphoma gene expression data to determine the identity of a particular lymphoma and to predict survival in a subject diagnosed with a particular lymphoma. This information will be useful in developing the therapeutic approach to be used with a particular subject.

1 . A method for predicting survival in a diffuse large B cell lymphoma (DLBCL) subject comprising the steps of:
 a) isolating gene expression product from a biopsy sample from a subject;   b) obtaining gene expression data for a set of genes in said biopsy sample, wherein the gene expression data includes expression levels of BMP6, proliferation gene expression signature genes, germinal center B cell gene expression signature genes, MHC class II gene expression signature genes, and lymph node gene expression signature genes;   c) determining an average gene expression level of genes in the proliferation gene expression signature to obtain a proliferation gene expression signature value;   d) determining an average gene expression level of genes in the germinal center B cell gene expression signature to obtain a germinal center B cell gene expression signature value;   e) determining an average gene expression level of genes in the MHC class II gene expression signature to obtain an MHC class II gene expression signature value;   f) determining an average gene expression level of genes in the lymph node gene expression signature to obtain a lymph node gene expression signature value;   g) measuring the expression level of BMP6 to obtain a BMP6 expression value;   h) determining a survival predictor score corresponding to: [0.241*(proliferation gene expression signature value)]+[0.310*(BMP6 expression value)]−[0.290*(germinal center B cell gene expression signature value)]−[0.311*(MHC class II gene expression signature value)]−[0.249*(lymph node gene expression signature value)], wherein a higher survival predictor score is associated with worse survival;   i) analyzing said sample for a gain or amplification in the 3p11-p12 region of chromosome 3, wherein a gain or amplification in said region is associated with worse survival.   
     
     
         2 . The method of  claim 1 , wherein said step of analyzing for a gain or amplification in the 3p11-p12 region of chromosome 3 is performed using comparative genomic hybridization. 
     
     
         3 . A method for predicting survival in a diffuse large B cell lymphoma (DLBCL) subject comprising the steps of:
 a) obtaining a biopsy sample from said subject; and   b) analyzing said sample for a gain or amplification in the 3p11-p12 region of chromosome 3;   
       wherein a gain or amplification in the 3p11-p12 region of chromosome 3 is associated with worse survival. 
     
     
         4 . The method of  claim 3 , wherein said step of analyzing for a gain or amplification in the 3p11-p12 region of chromosome 3 is performed using comparative genomic hybridization. 
     
     
         5 . The method of  claim 1 , wherein said step of analyzing for a gain or amplification in the 3p11-p12 region of chromosome 3 is performed using polymerase chain reaction (PCR). 
     
     
         6 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein said step of analyzing for a gain or amplification in the 3p11-p12 region of chromosome 3 is performed using real-time quantitative PCR. 
     
     
         13 . The method of  claim 1 , wherein said step of analyzing for a gain or amplification in the 3p11-p12 region of chromosome 3 is performed using cytogenetic analysis of bands in the 3p11-p12 region. 
     
     
         14 . The method of  claim 3 , wherein said step of analyzing for a gain or amplification in the 3p11-p12 region of chromosome 3 is performed using PCR. 
     
     
         15 . The method of  claim 3 , wherein said step of analyzing for a gain or amplification in the 3p11-p12 region of chromosome 3 is performed using real-time quantitative PCR. 
     
     
         16 . The method of  claim 3 , wherein said step of analyzing for a gain or amplification in the 3p11-p12 region of chromosome 3 is performed using cytogenetic analysis of bands in the 3p11-p12 region.