DIAGNOSTIC TESTS FOR PREDICTING PROGNOSIS, RECURRENCE, RESISTANCE OR SENSITIVITY TO THERAPY AND METASTATIC STATUS IN CANCER
First Claim
1. A novel molecular signature comprising of gene expression profile of a combination of two or more genes from the set ABCA1, ABCE1, ABCG1, ABHD12, ACLY, ACOT9, ACTA1, ACTL6A, ACTN1, ACTR1B, ACTR2, ADAM17, ADAM9, ADAR, AHR, AIM2, AKR1B1, AKTIP, ALG3, ALKBH7, AMD1, AMIGO2, AMMECR1L, ANKH, ANKRD11, ANKRD50, ANP32E, ANXA1, AP3S2, APLP2, APOBEC3A, APOE, APOL6, APP, ARF3, ARFIP1, ARFIP2, ARHGAP5, ARHGEF1, ARHGEF10L, ARL1, ARMC10, ARPC1B, ARSI, ARVCF, ASB8, ASPH, ATP2B4, ATP2C1, ATP6V0E1, ATP6V1C1, ATP8B1, ATR, AURKA, BAG1, BANF1, BASP1, BAZ1A, BAZ2B, BBC3, BCAM, BCAT1, BCL6, BCLAF1, BID, BMS1, BRD1, BSCL2, BUB3, BXDC5, CA13, CADM1, CALU, CAMSAP1L1, CAND1, CASP1, CASP7, CAV1, CBLB, CBX3, CCDC128, CCDC44, CCL18, CCNE1, CCNF, CDC25B, CDC27, CDC34, CDK6, CDKN2A, CEACAM1, CENTB2, CENTD1, CENTD2, CFB, CHFR, CHI3L1, CHMP6, CHST11, CHSY1, CHUK, CHURC1, CIDEB, CIRH1A, CKLF, CKM, CLCA4, CLCC1, CLCN7, CLDND1, CLEC7A, CLPP, CLPX, CMIP, CMTM4, COBL, COL4A1, COL4A2, COL5A1, COL5A2, COPE, COQ9, COTL1, COX15, CRYAB, CSDA, CSF2RB, CSGlcA-T, CSNK1A1, CSNK2A2, CSPG4, CTHRC1, CTNND1, CTSB, CTSC, CXCL10, CXCL16, CXCL9, CXXC5, CYBASC3, CYLD, CYP51A1, DCBLD1, DCLRE1C, DCXR, DDOST, DDX21, DDX, DDX54, DEPDC6, DERL1, DFNA5, DGKQ, DHRS7B, DLG7, DLGAP4, DPY19L3, DRAM, DTX3L, E2F3, EAF2, ECHDC2, ECOP, ECSIT, EFHD2, EGFL6, EIF2S3, EIF3G, EIF4E, EIF5, EMILIN2, EMP1, ENAH, ENSA, ENTPD6, EPSTI1, ERCC1, ERGIC2, ERGIC3, ERMP1, ETV6, EZH2, FAM101B, FAM116A, FAM122B, FAM122B, TMEM57, FAM125A, FAM135A, FAM33A, FAM38A, FAM3A, FAM80B, FAM89B, FAM91A1, FAT, FBLIM1, FBRS, FBXW5, FEZ1, FJX1, FKBP15, FKBP2, FKBP9, FLJ21438, FLJ35220, FLNB, FLRT2, FNDC3B, FOLR1, FOLR2, FOXJ2, FRMD4B, FRMD6, FSCN1, FST, FTSJ1, FUS, FUT7, GALNAC4S-6ST, GART, GASS, SNORD79, GBP6, GJA1, GLIPR, GLTP, GLTSCR2, GLUD1, GMD, GNAl2, GNB5, GNPTG, GOLGA8A, GPD1L, GPD2, GPR108, GPR137B, GPR172A, GPR176, GPR5, GPSM1, GREM1, GSDMDC1, GSK3A, GSPT1, GTF2A1, GZMB, H19, H2AFX, HAB1, HAX1, HBA1, HBA1, HBA2, HBA2, HBB, RAP1B, HEATR1, HEATR6, HERC5, HEXB, HIBCH, HIF1A, HINT2, HIPK1, HIST1H1C, HMCN2, HNRNPA2B1, HNRNPC, HNRPA3, HOPX, HRASLS, HRB, HSP90B1, HSPB8, HSPH1, HTRA1, ICT1, IDH3G, IF116, IFI30, IF16, IFIT3, IFNGR1, IGF2BP2, IGFBP5, IGH@, IGHG1, IGHG2, IGHG3, IGHM, IGHV4-31, IGK@, IGKC, IGKV1-5, IGKV2-24, IGLJ3, IGLV2-14, IGL@, IGLV325, IKZF2, IL10RB, IL1R1, IL8, IMP4, IMPDH1, IRAK1, IRF9, ITGA6, JAG2, JOSD3, KCNS3, KDELR2, KIAA0241, KIAA0494, KIAA0562, KIAA0746, KIAA0922, KIAA1468, KIAA1546, KIAA1598, KIDINS220, KIF21A, KIF3B, KIRREL, KLHL22, KPNA1, KPNA2, KPNA3, KRBA1, LAMC2, LAPTM5, LARP6, LASP1, LBR, LHFPL2, LIMA1, LMAN2, LMAN2L, LMNA, LMOD2, THAP4, LOC729604, LOX, LOXL2, LPCAT1, LRIG3, LRRC58, LRRC8D, LSG1, LTBP3, LY96, LYAR, MAGED1, MAGED4, MAGED4B, MAMDC2, MAML2, MAN2A1, MAN2B1, MAOB, MAP1LC3B, MAP4K5, MAPRE3, MARCKS, MARCKSL1, MARVELD1, MATR3, MAX, MAZ, MB, MEF2A, MEX3C, MFAP2, MFHAS1, MFSD5, MGC3196, MIB1, MIB2, MIER1, MINA, MIS12, MLLT11, MLSTD2, MLXIPL, MMP1, MMP10, MMP12, MMP13, MMP3, MMP9, MOBKL1A, MRPL48, MRPS18B, MTCP1, MTHFD2, MVP, MYBL2, MYL1, MYL2, MY010, MYO1B, N4BP1, NADK, NARS2, NAT10, NAV2, NBN, NCOA1, NDE1, NDRG2, NEK6, NETO2, NFAT5, NFATC2IP, NINJ1, NIPSNAP3A, NOL5A, NOTCH2, NPAT, NPEPL1, NPL, NQO1, NSFL1C, NUAK1, NUBP2, NUDCD1, NUDT22, NXT1, OAS2, OAS3, ODZ2, OFD1, OGT, OSTM1, OXA1L, PABPC1, PAFAH1B2, PAPD4, PARN, PCDHGA1, PCDHGA10, PCDHGA11, PCDHGA12, PCDHGA2, PCDHGA3, PCDHGA4, PCDHGA5, PCDHGA6, PCDHGA7, PCDHGA8, PCDHGA9, PCDHGB1, PCDHGB2, PCDHGB, PCDHGB4, PCDHGB5, PCDHGB6, PCDHGB7, PCDHGC3, PCDHGC4, PCDHGC5, PCTK2, PDCD2L, PDGFC, PDPN, PEMT, PET112L, PFN2, PGGT1B, PGS1, PHLDB1, PIK3CD, PIK3R4, PIP5K3, PKN2, PKP4, PLAU, PLEKHA5, PLEKHG5, PLK2, PLOD3, PLXDC2, PLXNA1, PNMA1, PNN, PNPLA2, PNPLA4, PNRC1, POLD4, POLR1D, POLR2G, POLR2J, POPS, PPAP2B, PPFIA1, PPIA, PPP1CA, PPP1CB, PPP2R1B, PRDM1, PRNP, PROCR, PRPF38A, PRSS23, PSMA3, PSMA4, PSMD8, PSME2, PSME3, PSMF1, PTCD1, PTHLH, PTPN2, PTPRE, PTPRK, PTPRZ1, PUS7, PXDN, PXMP4, RAB23, RAB31, RAB32, RABGAP1L, RABL5, RAD51C, RAPGEFL1, RAPH1, RASGEF1A, RBBP4, RBM17, RBM22, RBM25, RBMS1, RBMX, RBP1, RBP7, RC3H2, RDH11, REEP3, RER1, RFFL, RGS3, RGS4, RHBDF2, RHOQ, RHOU, RILP, RIN2, RIPK2, RNASEH2A, RNF12, RNF138, RNF145, RNF167, RP6, 213H19.1, RPN2, RPP25, RRAGD, RRAS2, RRP15, RSPRY1, RTP4, RUNX1, RYBP, SAC3D1, SART3, SCHIP1, SCRN1, SDAD1, SDF2, SDF4, SEC16A, SEC23B, SEC24A, SEC63, SEP15, SERPINB1, SERPINH1, SFPQ, SFRP1, SFRS12, SFRS2, SFRS7, SFXN3, SFXNS, SGMS2, SHARPIN, SHC1, SIRPA, SIXS, SKAP2, SLC16A3, SLC25A13, SLC26A2, SLC2A3P1, SLC30A7, SLC35B1, SLC39A14, SLC39A6, SLC44A2, SLC6A2, SLC7A6, SLN, SMPD1, SMPX, SMYD2, SNAI2, SNAPC1, SNX10, SOD3, SORT1, SOX15, SOX4, SP110, SP3, SPIRE1, SRP72, SRPK1, SRPK2, SRPR, SSSCA1, ST3GAL5, STAT1, STAT2, STAT3, STCH, STK38, STMN1, STRBP, SUDS3, SUSD4, SYNGR1, SYNJ2, TAF10, TAP2, TARBP2, TARS, TCERG1, TDG, TES, TEX10, TFTFCP2L1, TFE3, TGFB1I1, TGIF1, THAP11, THBS2, THEM2, THSD1, TIGDS, TIMM17B, TLR2, TMCC1, TMED10, TMED8, TMEM123, TMEM161B, TMEM170, TMEM184B, TMEM189, TMEM29, TMEM39B, TMEPAI, TMTC3, TNC, TNFAIP6, TNFRSF1A, TNFSF10, TNNC1, TNNT1, TOM1L1, TOPBP1, TP53I11, TP53INP1, TPBG, TPM1, TPM2, TPST1, TRABD, TRAM2, TRAPPC1, TREX1, TRIM22, TRIM38, TRIM47, TRIO, TRMT6, TUBA1C, TWF2, TXNDC1, TXNDC12, TXNDCS, UBE2L6, UBL3, UCK1, UCKL1, UFM1, UHRF1, URM1, USE1, USP1, USP34, USP53, UTP11L, VARS2, VPS24, VPS54, VRK3, WAPAL, WBP1, WDR45, WDR54, WDR68, WDR81, WEE1, WHSC1, XPOT, YBX1, YES1, YKT6, YRDC, ZCCHC17, ZFP64, ZMYM2, ZNF217, ZNF408, ZNF574, ZNFX1, ZSWIM6 or expression of proteins encoded by these genes in carcinoma tissues or tissue adjacent to the carcinoma tissue that is useful for personalizing cancer treatment.
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Abstract
The present invention describes a method utilizing a set of genes or gene products whose altered expression in cancer tissue, particularly head and neck cancer and other carcinomas, or its adjacent normal tissues predicts (a) probability of recurrence in time after treatment (b) sensitivity or resistance to therapies or (c) probability of metastasis at the time of initial discovery of the tumor. Furthermore, the invention describes methods of determining the molecular signature in tumor tissues, tissues adjacent to the tumor, or in saliva by using DNA microarray techniques, quantitative real-time PCR, immunohistochemistry or other methods that are used for determining gene or gene product expression levels.
11 Citations
7 Claims
- 1. A novel molecular signature comprising of gene expression profile of a combination of two or more genes from the set ABCA1, ABCE1, ABCG1, ABHD12, ACLY, ACOT9, ACTA1, ACTL6A, ACTN1, ACTR1B, ACTR2, ADAM17, ADAM9, ADAR, AHR, AIM2, AKR1B1, AKTIP, ALG3, ALKBH7, AMD1, AMIGO2, AMMECR1L, ANKH, ANKRD11, ANKRD50, ANP32E, ANXA1, AP3S2, APLP2, APOBEC3A, APOE, APOL6, APP, ARF3, ARFIP1, ARFIP2, ARHGAP5, ARHGEF1, ARHGEF10L, ARL1, ARMC10, ARPC1B, ARSI, ARVCF, ASB8, ASPH, ATP2B4, ATP2C1, ATP6V0E1, ATP6V1C1, ATP8B1, ATR, AURKA, BAG1, BANF1, BASP1, BAZ1A, BAZ2B, BBC3, BCAM, BCAT1, BCL6, BCLAF1, BID, BMS1, BRD1, BSCL2, BUB3, BXDC5, CA13, CADM1, CALU, CAMSAP1L1, CAND1, CASP1, CASP7, CAV1, CBLB, CBX3, CCDC128, CCDC44, CCL18, CCNE1, CCNF, CDC25B, CDC27, CDC34, CDK6, CDKN2A, CEACAM1, CENTB2, CENTD1, CENTD2, CFB, CHFR, CHI3L1, CHMP6, CHST11, CHSY1, CHUK, CHURC1, CIDEB, CIRH1A, CKLF, CKM, CLCA4, CLCC1, CLCN7, CLDND1, CLEC7A, CLPP, CLPX, CMIP, CMTM4, COBL, COL4A1, COL4A2, COL5A1, COL5A2, COPE, COQ9, COTL1, COX15, CRYAB, CSDA, CSF2RB, CSGlcA-T, CSNK1A1, CSNK2A2, CSPG4, CTHRC1, CTNND1, CTSB, CTSC, CXCL10, CXCL16, CXCL9, CXXC5, CYBASC3, CYLD, CYP51A1, DCBLD1, DCLRE1C, DCXR, DDOST, DDX21, DDX, DDX54, DEPDC6, DERL1, DFNA5, DGKQ, DHRS7B, DLG7, DLGAP4, DPY19L3, DRAM, DTX3L, E2F3, EAF2, ECHDC2, ECOP, ECSIT, EFHD2, EGFL6, EIF2S3, EIF3G, EIF4E, EIF5, EMILIN2, EMP1, ENAH, ENSA, ENTPD6, EPSTI1, ERCC1, ERGIC2, ERGIC3, ERMP1, ETV6, EZH2, FAM101B, FAM116A, FAM122B, FAM122B, TMEM57, FAM125A, FAM135A, FAM33A, FAM38A, FAM3A, FAM80B, FAM89B, FAM91A1, FAT, FBLIM1, FBRS, FBXW5, FEZ1, FJX1, FKBP15, FKBP2, FKBP9, FLJ21438, FLJ35220, FLNB, FLRT2, FNDC3B, FOLR1, FOLR2, FOXJ2, FRMD4B, FRMD6, FSCN1, FST, FTSJ1, FUS, FUT7, GALNAC4S-6ST, GART, GASS, SNORD79, GBP6, GJA1, GLIPR, GLTP, GLTSCR2, GLUD1, GMD, GNAl2, GNB5, GNPTG, GOLGA8A, GPD1L, GPD2, GPR108, GPR137B, GPR172A, GPR176, GPR5, GPSM1, GREM1, GSDMDC1, GSK3A, GSPT1, GTF2A1, GZMB, H19, H2AFX, HAB1, HAX1, HBA1, HBA1, HBA2, HBA2, HBB, RAP1B, HEATR1, HEATR6, HERC5, HEXB, HIBCH, HIF1A, HINT2, HIPK1, HIST1H1C, HMCN2, HNRNPA2B1, HNRNPC, HNRPA3, HOPX, HRASLS, HRB, HSP90B1, HSPB8, HSPH1, HTRA1, ICT1, IDH3G, IF116, IFI30, IF16, IFIT3, IFNGR1, IGF2BP2, IGFBP5, IGH@, IGHG1, IGHG2, IGHG3, IGHM, IGHV4-31, IGK@, IGKC, IGKV1-5, IGKV2-24, IGLJ3, IGLV2-14, IGL@, IGLV325, IKZF2, IL10RB, IL1R1, IL8, IMP4, IMPDH1, IRAK1, IRF9, ITGA6, JAG2, JOSD3, KCNS3, KDELR2, KIAA0241, KIAA0494, KIAA0562, KIAA0746, KIAA0922, KIAA1468, KIAA1546, KIAA1598, KIDINS220, KIF21A, KIF3B, KIRREL, KLHL22, KPNA1, KPNA2, KPNA3, KRBA1, LAMC2, LAPTM5, LARP6, LASP1, LBR, LHFPL2, LIMA1, LMAN2, LMAN2L, LMNA, LMOD2, THAP4, LOC729604, LOX, LOXL2, LPCAT1, LRIG3, LRRC58, LRRC8D, LSG1, LTBP3, LY96, LYAR, MAGED1, MAGED4, MAGED4B, MAMDC2, MAML2, MAN2A1, MAN2B1, MAOB, MAP1LC3B, MAP4K5, MAPRE3, MARCKS, MARCKSL1, MARVELD1, MATR3, MAX, MAZ, MB, MEF2A, MEX3C, MFAP2, MFHAS1, MFSD5, MGC3196, MIB1, MIB2, MIER1, MINA, MIS12, MLLT11, MLSTD2, MLXIPL, MMP1, MMP10, MMP12, MMP13, MMP3, MMP9, MOBKL1A, MRPL48, MRPS18B, MTCP1, MTHFD2, MVP, MYBL2, MYL1, MYL2, MY010, MYO1B, N4BP1, NADK, NARS2, NAT10, NAV2, NBN, NCOA1, NDE1, NDRG2, NEK6, NETO2, NFAT5, NFATC2IP, NINJ1, NIPSNAP3A, NOL5A, NOTCH2, NPAT, NPEPL1, NPL, NQO1, NSFL1C, NUAK1, NUBP2, NUDCD1, NUDT22, NXT1, OAS2, OAS3, ODZ2, OFD1, OGT, OSTM1, OXA1L, PABPC1, PAFAH1B2, PAPD4, PARN, PCDHGA1, PCDHGA10, PCDHGA11, PCDHGA12, PCDHGA2, PCDHGA3, PCDHGA4, PCDHGA5, PCDHGA6, PCDHGA7, PCDHGA8, PCDHGA9, PCDHGB1, PCDHGB2, PCDHGB, PCDHGB4, PCDHGB5, PCDHGB6, PCDHGB7, PCDHGC3, PCDHGC4, PCDHGC5, PCTK2, PDCD2L, PDGFC, PDPN, PEMT, PET112L, PFN2, PGGT1B, PGS1, PHLDB1, PIK3CD, PIK3R4, PIP5K3, PKN2, PKP4, PLAU, PLEKHA5, PLEKHG5, PLK2, PLOD3, PLXDC2, PLXNA1, PNMA1, PNN, PNPLA2, PNPLA4, PNRC1, POLD4, POLR1D, POLR2G, POLR2J, POPS, PPAP2B, PPFIA1, PPIA, PPP1CA, PPP1CB, PPP2R1B, PRDM1, PRNP, PROCR, PRPF38A, PRSS23, PSMA3, PSMA4, PSMD8, PSME2, PSME3, PSMF1, PTCD1, PTHLH, PTPN2, PTPRE, PTPRK, PTPRZ1, PUS7, PXDN, PXMP4, RAB23, RAB31, RAB32, RABGAP1L, RABL5, RAD51C, RAPGEFL1, RAPH1, RASGEF1A, RBBP4, RBM17, RBM22, RBM25, RBMS1, RBMX, RBP1, RBP7, RC3H2, RDH11, REEP3, RER1, RFFL, RGS3, RGS4, RHBDF2, RHOQ, RHOU, RILP, RIN2, RIPK2, RNASEH2A, RNF12, RNF138, RNF145, RNF167, RP6, 213H19.1, RPN2, RPP25, RRAGD, RRAS2, RRP15, RSPRY1, RTP4, RUNX1, RYBP, SAC3D1, SART3, SCHIP1, SCRN1, SDAD1, SDF2, SDF4, SEC16A, SEC23B, SEC24A, SEC63, SEP15, SERPINB1, SERPINH1, SFPQ, SFRP1, SFRS12, SFRS2, SFRS7, SFXN3, SFXNS, SGMS2, SHARPIN, SHC1, SIRPA, SIXS, SKAP2, SLC16A3, SLC25A13, SLC26A2, SLC2A3P1, SLC30A7, SLC35B1, SLC39A14, SLC39A6, SLC44A2, SLC6A2, SLC7A6, SLN, SMPD1, SMPX, SMYD2, SNAI2, SNAPC1, SNX10, SOD3, SORT1, SOX15, SOX4, SP110, SP3, SPIRE1, SRP72, SRPK1, SRPK2, SRPR, SSSCA1, ST3GAL5, STAT1, STAT2, STAT3, STCH, STK38, STMN1, STRBP, SUDS3, SUSD4, SYNGR1, SYNJ2, TAF10, TAP2, TARBP2, TARS, TCERG1, TDG, TES, TEX10, TFTFCP2L1, TFE3, TGFB1I1, TGIF1, THAP11, THBS2, THEM2, THSD1, TIGDS, TIMM17B, TLR2, TMCC1, TMED10, TMED8, TMEM123, TMEM161B, TMEM170, TMEM184B, TMEM189, TMEM29, TMEM39B, TMEPAI, TMTC3, TNC, TNFAIP6, TNFRSF1A, TNFSF10, TNNC1, TNNT1, TOM1L1, TOPBP1, TP53I11, TP53INP1, TPBG, TPM1, TPM2, TPST1, TRABD, TRAM2, TRAPPC1, TREX1, TRIM22, TRIM38, TRIM47, TRIO, TRMT6, TUBA1C, TWF2, TXNDC1, TXNDC12, TXNDCS, UBE2L6, UBL3, UCK1, UCKL1, UFM1, UHRF1, URM1, USE1, USP1, USP34, USP53, UTP11L, VARS2, VPS24, VPS54, VRK3, WAPAL, WBP1, WDR45, WDR54, WDR68, WDR81, WEE1, WHSC1, XPOT, YBX1, YES1, YKT6, YRDC, ZCCHC17, ZFP64, ZMYM2, ZNF217, ZNF408, ZNF574, ZNFX1, ZSWIM6 or expression of proteins encoded by these genes in carcinoma tissues or tissue adjacent to the carcinoma tissue that is useful for personalizing cancer treatment.
Specification