Methods for identifying, diagnosing, and predicting survival of lymphomas

Abstract

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 is useful in developing the appropriate therapeutic approach for use with a particular subject.

1 . A method for predicting survival in a follicular lymphoma (FL) subject comprising the steps of
 a) isolating gene expression product from a biopsy sample from a subject;   b) obtaining gene expression data from the isolated gene expression product, wherein the gene expression data comprises data for genes in an immune response-1 gene expression signature and genes in an immune response-2 gene expression signature;   c) obtaining an average gene expression level for the genes in the immune response-1 gene expression signature to thereby obtain an immune response-1 gene expression signature value;   d) obtaining an average gene expression level for the genes in the immune response-2 gene expression signature to thereby obtain an immune response-2 gene expression signature value; and   f) calculating a survival predictor score using an equation: [2.71*(immune response-2 gene expression signature value)]−[2.36*(immune response-1 gene expression signature value)]; wherein a higher survival predictor score is associated with worse survival.   
     
     
         2 . The method of  claim 1  wherein the step of obtaining gene expression data comprises use of a microarray. 
     
     
         3 . The method of  claim 1  wherein the immune response-1 gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1095985, 1096579, 1097255, 1097307, 1097329, 1097561, 1098152, 1098405, 1098548, 1098893, 1099053, 1100871, 1120196, 1101004, 1103303, 1107713, 1115194, 1119251, 1119838, 1119924, 1120267, 1121313, 1121406, 1121720, 1122956, 1123038, 1123092, 1123875, 1124760, 1128356, 1128395, 1132104, 1133408, 1134069, 1134751, 1134945, 1135743, 1135968, 1136048, 1136087, 1137137, 1137289, 1137534, 1139339, 1139461, 11400391, 140524, and 1140759. 
     
     
         4 . The method of  claim 1  wherein the immune response-2 gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1118755, 1118966, 1121053, 1121267, 1121331, 1121766, 1121852, 1122624, 1122679, 1122770, 1123767, 1123841, 1126097, 1126380, 1126628, 1126836, 1127277, 1127519, 1127648, 1128483, 1128818, 1129012, 1129582, 1129658, 1129705, 1129867, 1130003, 1130388, 1131837, 1133843, 1133949, 1134447, 1135117, 1136017, 1137478, 1137745, 1137768, 1138476, 1138529, 1138601, 1139862, 1140189, and 1140389. 
     
     
         5 . 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 from the isolated gene expression product, wherein the gene expression data comprises data for genes in an ABC DLBCL high gene expression signature, a lymph node gene expression signature, and an MHC class II gene expression signature;   c) obtaining an average gene expression level for the genes in the ABC DLBCL high gene expression signature to thereby obtain an ABC DLBCL high gene expression signature value;   d) obtaining an average gene expression level for the genes in the lymph node gene expression signature to thereby obtain a lymph node gene expression signature value;   e) obtaining an average gene expression level for the genes in the MHC class II gene expression signature to thereby obtain an MHC class II gene expression signature value;   f) calculating a survival predictor score using an equation: [0.586*(ABC DLBCL high gene expression signature value)]−[0.468*(lymph node gene expression signature value)]−[0.336*(MHC class II gene expression signature)]−[0.2006*(MHC class II gene expression signature value)]; wherein a higher survival predictor score is associated with worse survival.   
     
     
         6 . The method of  claim 5  wherein the step of obtaining gene expression data comprises use of a micro array. 
     
     
         7 . The method of  claim 5  wherein the ABC DLBCL gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1134271, 1121564, 1119889, 1133300, 1106030, 1139301, 1122131, 1114824, 1100161, and 1120129. 
     
     
         8 . The method of  claim 5  wherein the lymph node gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1097126, 1120880, 1098898, 1123376, 1128945, 1130994, 1124429, 1099358, 1130509, 1095985, 1123038, 1133700, 1122101, and 1124296. 
     
     
         9 . The method of  claim 5  wherein the MHC class II gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1123127, 1136777, 1137771, 1134281, 1136573, and 1132710. 
     
     
         10 . A method for predicting survival in a mantle cell lymphoma (MCL) subject comprising the steps of:
 a) isolating gene expression product from a biopsy sample from a subject;   b) obtaining gene expression data from the isolated gene expression product, wherein the gene expression data comprises data for genes in a proliferation gene expression signature;   c) averaging the gene expression level of genes from the proliferation gene expression signature to thereby obtain a proliferation gene expression signature value;   d) calculating a survival predictor score using an equation: [1.66*(proliferation gene expression signature value)]; wherein a higher survival predictor score is associated with worse survival.   
     
     
         11 . The method of  claim 10  wherein the step of obtaining gene expression data comprises use of a microarray. 
     
     
         12 . The method of  claim 10  wherein the proliferation gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1097290, 1101295, 1119729, 1120153, 1120494, 1124745, 1126148, 1130618, 1134753, 1139654, and 1140632. 
     
     
         13 . The method of  claim 10  wherein the proliferation gene expression signature comprises at least one gene selected from the group consisting of (listed by UNIQID): 1119294, 1119729, 1120153, 1121276, 1123358, 1124178, 1124563, 1130799, 1131274, 1131778, 1132449, 1135229, and 1136585.