Methods for identifying, diagnosing, and predicting survival of lymphomas

A method for treating a diffuse large B cell lymphoma (DLBCL) in a subject comprising:

• (a) isolating gene expression product from a DLBCL biopsy sample from a subject with DLBCL;
• (b) determining an average gene expression level of genes set forth in Table 2371 for the proliferation gene expression signature to obtain a proliferation gene expression signature value;
• (c) determining an average gene expression level of genes set forth in Table 2371 for the germinal center B cell gene expression signature to obtain a germinal center B cell gene expression signature value;
• (d) determining an average gene expression level of genes set forth in Table 2371 for the MHC class II gene expression signature to obtain an MHC class II gene expression signature value;
• (e) determining an average gene expression level of genes set forth in Table 2371 for the lymph node gene expression signature to obtain a lymph node gene expression signature value;
• (f) measuring the expression level of BMP6 to obtain a BMP6 expression value;
• (g) determining a survival predictor score calculated as [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 indicates worse survival, and a survival predictor score indicating a 5-year survival rate of 73% or less is calculated;
• (h) performing comparative genomic hybridization on a DLBCL biopsy sample from the subject to analyze for a gain or amplification in the 3p11-p12 region of chromosome 3, wherein a gain or amplification in said region is detected and indicates worse survival;
• and
• (i) administering cyclophosphamide, doxorubicine, vincristine, and prednisone to the subject to treat DLBCL in the subject.

A method for treating a diffuse large B cell lymphoma (DLBCL) in a subject comprising:

• (a) isolating gene expression product from a DLBCL biopsy sample from a subject with DLBCL;
• (b) determining an average gene expression level of genes set forth in Table 2371 for the proliferation gene expression signature to obtain a proliferation gene expression signature value;
• (c) determining an average gene expression level of genes set forth in Table 2371 for the germinal center B cell gene expression signature to obtain a germinal center B cell gene expression signature value;
• (d) determining an average gene expression level of genes set forth in Table 2371 for the MHC class II gene expression signature to obtain an MHC class II gene expression signature value;
• (e) determining an average gene expression level of genes set forth in Table 2371 for the lymph node gene expression signature to obtain a lymph node gene expression signature value;
• (f) measuring the expression level of BMP6 to obtain a BMP6 expression value;
• (g) determining a survival predictor score calculated as [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 indicates worse survival, and a survival predictor score indicating a 5-year survival rate of 73% or less is calculated;
• (h) performing cytogenetic analysis of bands in the 3p11-p12 region of chromosome 3 on a DLBCL biopsy sample from the subject to analyze for a gain or amplification in the 3p11-p12 region of chromosome 3, wherein a gain or amplification in said region is detected and indicates worse survival;
• and
• (i) administering cyclophosphamide, doxorubicine, vincristine, and prednisone to the subject to treat DLBCL in the subject.

A method for treating a diffuse large B cell lymphoma (DLBCL) in a subject comprising:

• (a) isolating gene expression product from a DLBCL biopsy sample from a subject with DLBCL;
• (b) determining an average gene expression level of genes set forth in Table 2371 for the proliferation gene expression signature to obtain a proliferation gene expression signature value;
• (c) determining an average gene expression level of genes set forth in Table 2371 for the germinal center B cell gene expression signature to obtain a germinal center B cell gene expression signature value;
• (d) determining an average gene expression level of genes set forth in Table 2371 for the MHC class II gene expression signature to obtain an MHC class II gene expression signature value;
• (e) determining an average gene expression level of genes set forth in Table 2371 for the lymph node gene expression signature to obtain a lymph node gene expression signature value;
• (f) measuring the expression level of BMP6 to obtain a BMP6 expression value;
• (g) determining a survival predictor score calculated as [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 indicates worse survival, and a survival predictor score indicating a 5-year survival rate of 73% or less is calculated;
• (h) performing polymerase chain reaction (PCR) on a DLBCL biopsy sample from the subject to analyze for a gain or amplification in the 3p11-p12 region of chromosome 3, wherein a gain or amplification in said region is detected and indicates worse survival;
• and
• (i) administering cyclophosphamide, doxorubicine, vincristine, and prednisone to the subject to treat DLBCL in the subject.