CLASSIFIERS OF NF-kB PATHWAY ACTIVATION, DEVICES, AND METHODS OF USE THEREOF

Abstract

This disclosure relates to classifiers of NF-κB pathway activation, devices, and methods of use thereof. In certain embodiments, the disclosure relates to methods comprising measuring changes in expression of genes controlled by p105 in a sample providing a detected p105 controlled gene expression pattern. In certain embodiments, the methods further comprise measuring changes in expression of genes controlled by p100 in a sample providing a detected p100 controlled gene expression pattern. In certain embodiments, the methods further comprise the step of comparing the detected p105 controlled gene expression patterns to a predetermined gene pattern and/or the detected p100 controlled gene expression patterns to a predetermined pattern.

1 . A method comprising measuring changes in expression of genes controlled by p105 in a sample providing a detected p105 controlled gene expression pattern. 
     
     
         2 . The method of  claim 1 , further comprising measuring changes in expression of genes controlled by p100 in a sample providing a detected p100 controlled gene expression pattern. 
     
     
         3 . The method of  claim 1 , further comprising the step of comparing the detected p105 and p100 controlled gene expression patterns to a predetermined gene pattern. 
     
     
         4 . The method of  claim 1 , wherein one of the samples is from a subject diagnosed with a disease. 
     
     
         5 . The method of  claim 4 , wherein the disease is cancer. 
     
     
         6 . The method of  claim 5 , wherein the disease is a lymphoma. 
     
     
         7 . The method of  claim 6 , wherein the disease is selected from a B cell neoplasm, T cell and natural killer cell neoplasm, multiple myeloma, and Hodgkin lymphoma. 
     
     
         8 . The method of  claim 1 , wherein measuring expression of genes controlled by p105 comprises detecting the changes in expression of three or more genes selected from, four or more genes selected from, or five or more genes selected from EXD3, BIRC7, HLA-F, PBK, DHFR, ECT2, and CCDC99. 
     
     
         9 . The method of  claim 2 , wherein measuring expression of genes controlled by p100 comprises detecting the changes in expression of three or more genes selected from, four or more genes selected from, or five or more genes selected from NIP7, COX11, HSPD1, EIF4E, NFE2L1, JUNB, and RASSF4. 
     
     
         10 . The method of  claim 8 , wherein measuring expression of genes controlled by p105 further comprises detecting the changes in expression of three or more genes selected from, four or more genes selected from, five or more genes selected from, six or more genes selected from, seven or more genes selected from, eight or more genes selected from, nine or more genes selected from, ten or more genes selected from, eleven or more genes selected from, twelve or more genes selected from, thirteen or more genes selected from, fourteen or more genes selected from, or fifteen or more genes selected from HLA-F, HLA-E, ICAM-1, ZFAND3, LMNA, FAM65A, EXD3, SYNPO, TNS4, NFE2L1, NCOA1, JUNB, RASSF4, C2, PLXND1, DENND3, PPARD. 
     
     
         11 . The method of  claim 9 , wherein measuring expression of genes controlled by p100 comprises detecting the changes in expression of three or more genes selected from, four or more genes selected from, five or more genes selected from, six or more genes selected from, seven or more genes selected from, eight or more genes selected from, nine or more genes selected from, ten or more genes selected from, eleven or more genes selected from, twelve or more genes selected from, thirteen or more genes selected from, fourteen or more genes selected from, fifteen or more genes selected from, sixteen or more genes selected from, or seventeen or more genes selected from EIF4E, SFRS3, SEH1L, SETMAR, USP1, DNAJC9, BRIX1, CCDC99, FAM29A, MCM10, C12orf48, PBK, MSH2, DHFR, CCNA2, MAD2L1, KIF11, and ECT2. 
     
     
         12 . The method of  claim 1 , further comprising the step of recording a normal, decreased, or increased expression of the genes. 
     
     
         13 . The method of  claim 12 , further comprising the step of reporting the recorded expression to a medical professional, medical institution, or a subject from which the sample was obtained or representative thereof. 
     
     
         14 . The method of  claim 1 , further comprising the step of administering antibody against CD20 in the event that the detected p105 controlled gene expression pattern indicates a canonical NF-κB activation pattern. 
     
     
         15 . The method of  claim 14 , wherein the antibody against CD20 is rituximab. 
     
     
         16 . The method of  claim 14 , wherein the antibody against CD20 is administered in combination with another anticancer agent. 
     
     
         17 . A device comprising hybridization probes for detecting measuring expression of genes controlled by p105. 
     
     
         18 . A device comprising hybridization probes for detecting measuring expression of genes controlled by p100. 
     
     
         19 . The device of  claim 17 , wherein said hybridization probes consist essentially of oligonucleotide sequences for HLA-F, HLA-E, ICAM-1, ZFAND3, LMNA, FAM65A, EXD3, SYNPO, TNS4, NFE2L1, NCOA1, JUNB, RASSF4, C2, PLXND1, DENND3, and PPARD genes. 
     
     
         20 . The device of  claim 18 , wherein said hybridization probes consist essentially of oligonucleotide sequences for EIF4E, SFRS3, SEH1L, SETMAR, USP1, DNAJC9, BRIX1, CCDC99, FAM29A, MCM10, C12orf48, PBK, MSH2, DHFR, CCNA2, MAD2L1, KIF11, and ECT2 genes. 
     
     
         21 . A kit comprising the devices of  claim 17 . 
     
     
         22 . The kit of  claim 21 , further comprising solutions for nucleic acid isolation, reverse-transcription, amplification, labeling, hybridization and washing to remove unhybridized material.