Method for subtyping lymphoma types by means of expression profiling
The invention is directed to methods for selecting a treatment option for an activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) subject, a germinal center B cell-like diffuse large B cell lymphoma (GCB DLBCL) subject, a primary mediastinal B cell lymphoma (PMBL) subject, a Burkitt lymphoma (BL) subject, or a mantle cell lymphoma (MCL) subject by analyzing digital gene expression data obtained from the subject, e.g., from a biopsy sample.
1. A method for treating an activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) in a human subject, a germinal center B cell-like diffuse large B cell lymphoma (GCB DLBCL) in a human subject, a primary mediastinal B cell lymphoma (PMBL) in a human subject, a Burkitt lymphoma (BL) in a human subject, or a mantle cell lymphoma (MCL) in a human subject, the method comprising:
(a) isolating RNA gene expression product from a biopsy sample from a lymphoma human subject;
(b) obtaining digital gene expression data from the isolated gene expression product, wherein the digital gene expression data comprises data for genes in a gene expression signature, and wherein the gene expression signature comprises each of the genes below:
Gene
GenBank Accession No.
ACSL5
NM_016234.3
ADAM12
NM_003474.4
AHCYL2
NM_001130723.2
AHR
NM_001621.3
AKAP2
NM_001136562.2
AKAP9
NM_005751.3
ALOX5
NM_000698.2
ANKRD13A
NM_033121.1
ANTXR1
NM_018153.3
ARID3A
NM_005224.2
ARID3B
NM_006465.2
ASB13
NM_024701.3
ATXN7L2
NM_153340.4
AUH
NM_001698.2
AUTS2
NM_001127231.1
BANK1
NM_001083907.1
BATF
NM_006399.3
BCAT1
NM_005504.4
BCL2
NM_053056.2
BCL2A1
NM_004049.2
BCL2L10
NM_020396.2
BCL6
NM_001706.2
BIRC3
NM_001165.3
BPGM
NM_199186.1
BPNT1
NM_006085.4
BSPRY
NM_017688.2
BUB1B
NM_001211.4
C10orf18
NM_017782.3
C13orf18
NM_025113.2
C3orf37
NM_020187.2
CALD1
NM_033138.2
CARD11
NM_032415.2
CCDC50
NM_174908.3
CCL17
NM_002987.2
CCND1
NM_053056.2
CCND2
NM_001759.2
CCR7
NM_001838.2
CD44
NM_000610.3
CDH11
NM_001797.2
CDK5RAP2
NM_001011649.1
CDK6
NM_001259.5
CFLAR
NM_003879.3
CGNL1
NM_032866.3
CHD4
NM_001273.2
CLIP2
NM_003388.4
CPA6
NM_001127445.1
CPNE3
NM_003909.2
CR2
NM_001006658.1
CREB3L2
NM_194071.2
CSF2RA
NM_006140.3
CSTA
NM_005213.3
CTHRC1
NM_138455.2
CTSH
NM_148979.2
CTSK
NM_000396.2
CYB5R2
NM_016229.3
CYP27A1
NM_000784.3
DAZAP2
NM_014764.3
DCTD
NM_001012732.1
DENND4A
NM_005848.3
DNAJB12
NM_017626.4
DNAJC10
NM_018981.1
DOCK10
NM_014689.1
DPYSL3
NM_001387.2
E2F2
NM_004091.2
EEPD1
NM_030636.2
EFEMP2
NM_016938.3
ELL2
NM_012081.5
EML1
NM_004434.2
ENTPD1
NM_001776.4
ERBB2IP
NM_018695.2
ERP29
NM_001034025.1
ETV6
NM_001987.4
FAM108C1
NM_021214.1
FAM159A
NM_001042693.1
FAM171B
NM_177454.3
FAM46C
NM_017709.3
FAM69A
NM_001006605.3
FAP
NM_004460.2
FAS
NM_000043.3
FBXO41
NM_001080410.1
FCER2
NM_002002.4
FKBP11
NM_016594.2
FLJ42418
NM_001001695.1
FN1
NM_212482.1
FNDC1
NM_032532.2
FUT8
NM_004480.3
GCET2
NM_001008756.1
GIT2
NM_057169.2
GNA13
NM_006572.4
GNL3
NM_014366.4
GORASP1
NM_031899.2
GSK3B
NM_002093.2
GYPC
NM_016815.2
HARBI1
NM_173811.3
HCK
NM_002110.2
HDAC1
NM_004964.2
HDGF
NM_004494.2
HEG1
NM_020733.1
HLA-DMA
NM_006120.3
HOMER2
NM_004839.2
HOPX
NM_001145460.1
HPCAL1
NM_134421.1
HSP90AA1
NM_005348.3
HSP90B1
NM_003299.1
HSPA9
NM_004134.4
HSPB8
NM_014365.2
HTRA1
NM_002775.4
ICAM1
NM_000201.1
IFIH1
NM_022168.2
IGSF3
NM_001542.2
IK
NM_006083.3
IL12A
NM_000882.2
IL13RA1
NM_001560.2
IL16
NM_004513.4
IL17RB
NM_018725.3
IRF4
NM_002460.1
ISG15
NM_005101.3
ISY1
NM_020701.2
ITGAV
NM_002210.2
ITGAX
NM_000887.3
ITGB2
NM_000211.2
ITPKB
NM_002221.3
JAK2
NM_004972.2
JAK3
NM_000215.2
KCNK12
NM_022055.1
KIAA0746
NM_015187.3
KIAA1274
NM_014431.2
KLHL5
NM_015990.4
KRAS
NM_033360.2
KYNU
NM_003937.2
LANCL1
NM_006055.1
LDHA
NM_005566.1
LIMA1
NM_001113547.1
LIMD1
NM_014240.2
LMO2
NM_005574.3
LRMP
NM_006152.2
LRRC15
NM_001135057.2
LRRC33
NM_198565.1
LTBP2
NM_000428.2
LYPD6B
NM_177964.3
LYZ
NM_000239.2
MAL
NM_002371.2
MAML3
NM_018717.4
MAP3K1
NM_005921.1
MAP4K4
NM_004834.3
MAPK10
NM_002753.2
MARCKSL1
NM_023009.5
MAST2
NM_015112.1
MDFIC
NM_199072.2
MLL2
NM_003482.3
MLLT10
NM_004641.2
MME
NM_000902.2
MMP2
NM_004530.2
MMP9
NM_004994.2
MOBKL2C
NM_145279.4
MPEG1
XM_937323.1
MTHFD2
NM_006636.3
MYB
NM_005375.2
MYBL1
XM_034274.14
MYC
NM_002467.3
NAIF1
NM_197956.3
NANS
NM_018946.3
NCF2
NM_000433.2
NECAP2
NM_018090.4
NEIL1
NM_024608.2
NEK6
NM_014397.3
NEU3
NM_006656.5
NFIL3
NM_005384.2
NFKBIZ
NM_001005474.1
NIPA2
NM_001008860.1
NOC3L
NM_022451.9
NOL5A
NM_006392.2
NP
NM_000270.3
OPA1
NM_130837.1
OSBPL3
NM_145320.1
PAG1
NM_018440.3
PDE9A
NM_001001567.1
PDIA5
NM_006810.2
PDLIM1
NM_020992.2
PDPN
NM_006474.4
PFTK1
NM_012395.2
PHF16
NM_014735.3
PHF23
NM_024297.2
PIM1
NM_002648.2
PIM2
NM_006875.2
PLAU
NM_002658.2
PLEK
NM_002664.2
PLEKHF2
NM_024613.2
PMEPA1
NM_020182.3
PPA1
NM_021129.3
PPP3CC
NM_005605.3
PRDX2
NM_005809.4
PRICKLE1
NM_153026.1
PRKCB
NM_212535.1
PRPSAP2
NM_002767.2
PRR6
NM_181716.2
PTGIR
NM_000960.3
PTK2
NM_005607.3
PTPN1
NM_002827.2
PTRH1
NM_001002913.1
R3HDM1
NM_015361.2
RAB20
NM_017817.1
RAB33A
NM_004794.2
RAB7L1
NM_001135664.1
RANBP9
NM_005493.2
RAPGEF5
NM_012294.3
RARRES2
NM_002889.3
RASGRP3
NM_015376.2
RC3H2
NM_018835.2
RCL1
NM_005772.3
REL
NM_002908.2
RFTN1
NM_015150.1
RGS9
NM_003835.1
RHOF
NM_019034.2
RNF214
NM_207343.2
RNUXA
NM_032177.3
ROBO1
NM_002941.2
RRP1B
NM_015056.2
S100Z
NM_130772.3
S1PR2
NM_004230.2
SACS
NM_014363.4
SAMSN1
NM_022136.3
SCARA5
NM_173833.4
SERPINA9
NM_001042518.1
SGK1
NM_005627.2
SH3BP5
NM_001018009.2
SIDT1
NM_017699.2
SLA
NM_001045556.2
SLAMF1
NM_003037.2
SLC38A5
NM_033518.2
SMARCA4
NM_003072.3
SNN
NM_003498.4
SNX11
NM_152244.1
SNX22
NM_024798.2
SNX29
NM_001080530.2
SOX11
NM_003108.3
SPARC
NM_003118.2
SPINK2
NM_021114.2
SPINT2
NM_021102.2
SPRED2
NM_181784.2
SSBP2
NM_012446.2
STAMBPL1
NM_020799.2
STAP1
NM_012108.2
STAT3
NM_139276.2
STK17A
NM_004760.1
STS
NM_000351.4
STX11
NM_003764.3
SUFU
NM_016169.2
SULF1
NM_015170.2
TARS
NM_152295.3
TBC1D9
NM_015130.2
TCF3
NM_003200.2
TCF4
NM_001083962.1
TCTN3
NM_015631.5
TERT
NM_198253.1
TEX9
NM_198524.1
THBS2
NM_003247.2
THOC5
NM_001002878.1
THY1
NM_006288.2
TIAM2
NM_001010927.2
TICAM2
NM_021649.4
TLE4
NM_007005.3
TLK1
NM_012290.3
TLR7
NM_016562.3
TMEM119
NM_181724.2
TMOD1
NM_003275.2
TNFRSF13B
NM_012452.2
TNFRSF17
NM_001192.2
TNFSF4
NM_003326.2
TOX
NM_014729.2
TPM1
NM_000366.5
TRAF1
NM_005658.3
TRIM56
NM_030961.1
TRIM62
NM_018207.2
TRIP13
NM_004237.2
TTC9
NM_015351.1
TUBB2C
NM_006088.5
UBXN4
NM_014607.3
USP12
NM_182488.3
USP46
NM_022832.2
VAC14
NM_018052.3
VASH2
NM_024749.3
VGLL4
NM_001128220.1
VRK3
NM_016440.3
WAC
NM_100486.2
WDR55
NM_017706.4
WNT3
NM_030753.3
XBP1
NM_005080.2
ZBTB32
NM_014383.1
ZBTB37
NM_001122770.1
ZBTB8
NM_001040441.1
ZCCHC2
NM_017742.4
ZCCHC7
NM_032226.2
ZNF281
NM_012482.3
ZNF318
NM_014345.2
ZNF598
NM_178167.2
ZNF608
NM_020747.2;
(c) optionally obtaining digital gene expression data from a first and second reference set of probe sets, the first and second reference set of probe sets being known for classifying ABC DLBCL, GCB DLBCL, PMBL, BL, or MCL;
(d) calculating a predictor score using an equation:
y
i
=
log
2
(
x
i
)
-
∑
j
log
2
(
x
j
)
h
j
-
log
2
(
r
i
)
+
log
2
(
g
i
)
wherein y i is a predictor score for gene i, x i is the counts for probe set i for gene i on the sample being tested, x j is the counts for probe set j for gene j, probe set j is the set of normalization genes of the sample being tested, h j is the normalization weight for probe set j as listed below:
Normalization
Gene
weights
ACPP
0
ACTG2
0
ADAM12
0
ADAM28
0
ADH1B
0
ADIPOQ
0
ADO
0
AHR
0
AICDA
0
AKAP2
0
AKR1C2
0
ALOX5
0
AMIGO2
0
ANKRD13A
0
ANLN
0
ANO3
0
ANTXR1
0
ANUBL1
0
APOL1
0
ARID3A
0
ARID3B
0
ARID5A
0
ARL6IP1
0
ARNT2
0
ARNTL
0
ASB13
0
ASPM
0
ATF3
0
ATM
0
ATP6V0E1
0
AUH
0
AURKA
0
AUTS2
0
BANK1
0
BASP1
0
BATF
0
BATF3
0
BCAT1
0
BCL10
0
BCL2
0
BCL2
0
BCL2
0
BCL2
0
BCL2
0
BCL2
0
BCL2A1
0
BCL2L10
0
BCL6
0
BEST3
0
BIRC2
0
BIRC3
0
BIRC5
0
BMP7
0
BPGM
0
BPNT1
0
BSPRY
0
BST2
0
BTBD19
0
BTG1
0
BTG2
0
BTK
0
BUB1
0
BUB1B
0
C10orf18
0
C13orf18
0
C15orf41
0
C3orf37
0
C5AR1
0
C5orf41
0
C7orf68
0
CACNA1D
0
CALD1
0
CAMK2B
0
CARD11
0
CAV1
0
CAV2
0
CCDC50
0
CCDC75
0
CCL17
0
CCNA2
0
CCNB1
0
CCNB2
0
CCND1
0
CCND1
0
CCND1
0
CCND1
0
CCND1
0
CCND1
0
CCND2
0
CCND3
0
CCR7
0
CD2
0
CD200
0
CD22
0
CD247
0
CD274
0
CD3D
0
CD3E
0
CD3G
0
CD40
0
CD44
0
CD47
0
CD5
0
CD58
0
CD6
0
CD74
0
CD79A
0
CD79B
0
CD8A
0
CD8B
0
CDC20
0
CDC25B
0
CDC25C
0
CDCA3
0
CDCA5
0
CDCA8
0
CDH11
0
CDC2
0
PFTK1
0
CDK4
0
CDK6
0
CDKN2A
0
CDKN2A
0
CDKN3
0
CELSR1
0
CENPA
0
CENPE
0
CENPF
0
CENPN
0
PRR6
0
CEP55
0
CFLAR
0
CGNL1
0
CIITA
0
CKS2
0
CLIP2
0
CLMN
0
CPNE3
0
CR2
0
CREB3L2
0
CREBBP
0
CSF2RA
0
CSTA
0
CTGF
0
CTH
0
CTHRC1
0
CTLA4
0
CTNNA2
0
CTPS
0
CTSH
0
CTSK
0
CXCL10
0
CXCL12
0
CXCL9
0
CYB5R2
0
CYP27A1
0
CYP2J2
0
CYSLTR1
0
DCBLD1
0
DCTD
0
DDAH2
0
DDX58
0
DENND4A
0
DCL1
0
DLEU1
0
DLGAP5
0
DNAJA1
0
DNAJB9
0
DNAJC10
0
DNMT3A
0
DOCK10
0
DPY19L1
0
DPYSL3
0
DRAM
0
DTX1
0
E2F2
0
E2F8
0
EBV_BZLF1
0
EBV_EBER1
0
EBV_EBER2
0
EBV_EBN_A1_CDS
0
EBV EBNA2_3′_end
0
EBV_EBNA2_long
0
EBV_EBNA3A
0
EBV_EBNA3B
0
EBV_EBNA3C
0
EBV_LMP1_3′_end
0
EBV_LMP1_unique
0
EBV_LPM2A
0
EEPD1
0
EFEMP2
0
EGFL7
0
EHD2
0
EIF5AL1
0
ELL2
0
EML1
0
EMR1
0
ENO1
0
ENPP3
0
ENTPD1
0
EP300
0
EPHB1
0
EPSTI1
0
ERG
0
ERP29
0
TXNDC4
0
ESPL1
0
ETV6
0
EXO1
0
FABP4
0
FAM108C1
0
FAM159A
0
FAM171B
0
FAM46C
0
FAM69A
0
FAM83D
0
FAP
0
FAS
0
FBP2
0
FBXO10
0
FBXO11
0
FCER2
0
FEZ1
0
FGL2
0
FKBP11
0
FKBP2
0
FLJ42418
0
FLNA
0
FN1
0
FNBP1
0
FNDC1
0
FOXM1
0
FOXO1
0
FOXP1
0
FSCN1
0
FUT8
0
FYB
0
GBP1
0
GBP4
0
GCET2
0
GGT1
0
GHR
0
GLDC
0
GLRX
0
GNA13
0
GNB4
0
GNG10
0
GNL3
0
GPR116
0
GPR176
0
GPR183
0
GRAMD1B
0
GRB10
0
GRSF1
0
GTSE1
0
GLT8D4
0
GYPC
0
H2AFV
0
H2AFX
0
HCK
0
HDAC1
0
HDAC2
0
HDGF
0
HEG1
0
HHV8_BCL2 homologue
0
HHV8_K1-32_Bcb_K1_protein
0
HHV8_ORF73-LANA
0
HHV8_T0.7/P6
0
HHV8_T1.1
0
HHV8_vFLIP_ORF71
0
HHV8_vIL6
0
HHV8_vMIP1b_ORFK4.2_KIE-3
0
HJURP
0
HLA-A
0
HLA-B
0
HLA-C
0
HLA-DMA
0
HLA-DPA1
0
HLA-DPB1
0
HLA-DQA1
0
HLA-DRA
0
HLA-E
0
HLA-F
0
HOMER2
0
HOPX
0
HPCAL1
0
HSP90B1
0
HSPB8
0
HTRA1
0
HYOU1
0
ICAM1
0
ID1
0
ID2
0
ID3
0
IDS
0
IER3
0
IFI16
0
IFI35
0
IFI44L
0
IFI6
0
IFIH1
0
IFIT1
0
IFIT2
0
IFIT3
0
IFITM1
0
IFNAR1
0
IFNAR2
0
IFNB1
0
IgA2_constant_region
0
IgE_constant_region
0
IGFBP5
0
IgG2_constant_region
0
IgG4_constant_region
0
IGSF3
0
IL10
0
IL12A
0
IL13
0
IL13RA1
0
IL16
0
IL17RB
0
IL4I1
0
IL6
0
ING1
0
INPP5D
0
IRAK1
0
IRAK2
0
IRAK3
0
IRAK4
0
IRF1
0
IRF3
0
IRF4
0
IRF5
0
IRF7
0
ISG15
0
ITGA9
0
ITGAV
0
ITGAX
0
ITGB2
0
ITPKB
0
JAK1
0
JAK2
0
JAK3
0
KCNJ1
0
KCNK12
0
KCNMA1
0
JMJD2C
0
KDR
0
KIAA1147
0
KIAA1274
0
KIF11
0
KIF14
0
KIF15
0
KIF18A
0
KIF18B
0
KIF20A
0
KIF23
0
KIF2C
0
KIF4A
0
KLHL5
0
KPNA2
0
KYNU
0
LAMB1
0
LAMP3
0
LANCL1
0
LAT
0
LAT2
0
LDHA
0
LHFPL3
0
LHX2
0
LIMA1
0
LIMD1
0
LMAN2
0
LMO2
0
LOC643529
0
LOXL2
0
LPCAT3
0
LRMP
0
LRPPRC
0
LRRC15
0
LRRC33
0
LTBP2
0
LYPD6B
0
LYZ
0
MACROD2
0
MAL
0
MALT1
0
MAML3
0
MAP3K1
0
MAP3K8
0
MAP4K4
0
MAPK10
0
MAPKAPK5
0
MARCKS
0
MARCKSL1
0
MAST2
0
MATR3
0
MCL1
0
MCM10
0
MCM7
0
MDFIC
0
MDM2
0
MFAP5
0
MFNG
0
MFSD2A
0
MGC87042
0
MIR17HG
0
MKI67
0
MME
0
MMP1
0
MMP2
0
MMP9
0
MMRN2
0
MNDA
0
MOBKL2C
0
MPEG1
0
MS4A1
0
MST1R
0
MTHFD2
0
MUC16
0
MYB
0
MYBL1
0
MYC
0
MYD88
0
MYO7A
0
FAM128B
0
NANS
0
NASP
0
NBN
0
NCAPG
0
NCAPH
0
NCF2
0
NCRNA00158
0
NDST4
0
NECAP2
0
NEIL1
0
NEK6
0
NFATC1
0
NFIL3
0
NFKBIA
0
NFKBIZ
0
NIPA2
0
NOC3L
0
NOL14
0
NOL5A
0
NOTCH1
0
NOTCH2
0
NUF2
0
NUP62
0
NUSAP1
0
OAS2
0
OAS3
0
OPN3
0
OSBPL3
0
PA2G4
0
PAG1
0
DKFZP564O0823
0
PAX6
0
PCNA
0
PDCD1LG2
0
PDE9A
0
PDGFRA
0
PDIA4
0
PDIA5
0
PDK4
0
PDLIM1
0
PDLIM3
0
PDPN
0
PECAM1
0
PECR
0
PGAM1
0
PHC3
0
PHF16
0
PIK3CA
0
PIK3CD
0
PIM1
0
PIM2
0
PLAU
0
PLEK
0
PLEKHF2
0
PLEKHG4B
0
PLXNB1
0
PMEPA1
0
PMP22
0
NP
0
POU2AF1
0
POU2F1
0
POU2F2
0
PPA1
0
PPP2R3B
0
FAM152B
0
PRDM1
0
PRDM12
0
PRDX2
0
PRDX4
0
PRICKLE1
0
PRKCB
0
PRMT1
0
PRPSAP2
0
PRSS1
0
PSMG1
0
PTEN
0
PTGER4
0
PTGIR
0
PTK2
0
PTPN1
0
PTPRB
0
PVRL1
0
PXDN
0
OSOX1
0
RAB31
0
RAB33A
0
RAB3A
0
RAB7L1
0
RAPGEF5
0
RARRES2
0
RASGRP3
0
RASSF4
0
RBCK1
0
RCL1
0
REL
0
RFTN1
0
RGL1
0
RGS9
0
RHEBL1
0
RHOF
0
RHOXF1
0
RNASEH2B
0
RNF31
0
RNGTT
0
ROBO1
0
ROBO4
0
RPN2
0
RPS6KA5
0
RSAD2
0
RTCD1
0
RUNDC2B
0
RXRA
0
S100Z
0
S1PR2
0
SAA1
0
SACS
0
SAE1
0
SAMSN1
0
SAP30
0
SCARA5
0
SDC1
0
SDCCAG8
0
KIAA0746
0
SEMA7A
0
SEPHS1
0
SERBP1
0
SERPINA9
0
SERPINB1
0
SFN
0
SFPQ
0
SGK1
0
SGOL2
0
SH2D1A
0
SH3BP5
0
SHARPIN
0
SIDT1
0
SIRPA
0
SIRPB1
0
SLA
0
SLAMF1
0
SLC12A8
0
SLC16A9
0
SLC1A4
0
SLC31A1
0
SLC35E2B
0
SLC38A5
0
SMAD1
0
SMAD7
0
SMARCA4
0
SNAP23
0
SNN
0
SNX11
0
SNX22
0
SNX29
0
SOCS1
0
SOCS2
0
SOCS3
0
SORBS1
0
SOX11
0
SOX5
0
SPAG5
0
SPARC
0
SPARCL1
0
SPIB
0
SPINK2
0
SPINT2
0
SPON1
0
SPRED2
0
SPRY1
0
SRPK1
0
SRPX
0
SRSF1
0
SSBP2
0
STAG3
0
STAMBPL1
0
STAP1
0
STAT1
0
STAT3
0
STEAP1
0
STK17A
0
STK38L
0
STMN1
0
STS
0
STX11
0
SULF1
0
SYK
0
SYPL1
0
SYT17
0
SYTL4
0
TARS
0
TAX1BP1
0
TBC1D27
0
TBC1D9
0
TCF3
0
TCF4
0
TCTN3
0
TEAD1
0
TEK
0
TERT
0
TEX9
0
TFDP2
0
TFPI2
0
TGFBR1
0
THBS2
0
THY1
0
TIAM2
0
TICAM2
0
TJP2
0
TK1
0
TLE4
0
TLK1
0
TLR7
0
TM4SF1
0
TMBIM6
0
TMEM109
0
TMEM119
0
TMOD1
0
TMPRSS6
0
TNF
0
TNFAIP2
0
TNFAIP3
0
TNFRSF13B
0
TNFRSF14
0
TNFRSF17
0
TNFRSF19
0
TNFSF10
0
TNFSF4
0
TNIP2
0
TNXB
0
TOP2A
0
TOX
0
TP53
0
TP73
0
TPM1
0
TPX2
0
TRAF1
0
TRAF3
0
TRIM25
0
TRIM6-TRIM34
0
TRIP13
0
TTC9
0
TUBG1
0
TXN
0
TXNDC5
0
TYK2
0
TYMS
0
UBE2I
0
UBE2S
0
USP12
0
USP18
0
USP46
0
VASH2
0
VGLL4
0
TMEM49
0
VWF
0
WASF1
0
WDR25
0
WHSC1
0
WNT3
0
XAF1
0
XBP1
0
YPEL1
0
ZAP70
0
ZBTB32
0
ZBTB38
0
ZBTB8
0
ZCCHC7
0
ZFP36L1
0
ZMYND8
0
ZNF238
0
ZNF281
0
ZNF318
0
ZNF385B
0
ZNF608
0
ZNRF1
0
ZPBP2
0
ZWINT
0
A2LD1
0
ABCA12
0
ACSL5
0.021276596
AHCYL2
0.021276596
AKAP9
0.021276596
ASCL2
0
ASMTL-AS1
0
ATOH8
0
ATXN7L2
0.021276596
C19orf26
0
C4orf31
0
CA7
0
CAMKK1
0
CDK5RAP2
0.021276596
CHD4
0.021276596
CHST5
0
CPA6
0
DAZAP2
0.021276596
DCLK3
0
DNAJB12
0.021276596
ERBB2IP
0.021276596
ERN2
0
KIAA0574
0
FAR2
0
FARP1
0
FBXL13
0
FBXO36
0
FBXO41
0.021276596
FCN2
0
GAD2
0
GATA1
0
GATA2
0
GIT2
0.021276596
GNG4
0
GORASP1
0.021276596
GSK3B
0.021276596
GYG2
0
H1FOO
0
HARBI1
0.021276596
HHIP
0
HSP90AA1
0.021276596
HSPA12B
0
HSPA9
0.021276596
IK
0.021276596
ISY1
0.021276596
KCNQ3
0
KCP
0
KIF6
0
KRAS
0.021276596
LRP3
0
MLL2
0.021276596
MLLT10
0.021276596
MSX2
0
KIAA0774
0
NAIF1
0.021276596
NEBL
0
NEU3
0.021276596
NHLH2
0
NRG1
0
OPA1
0.021276596
PDE4DIP
0
RNUXA
0.021276596
PHF23
0.021276596
PMCHL1
0
PNLIP
0
PPP3CC
0.021276596
PTENP1
0
PTPN21
0
PTRH1
0.021276596
R3HDM1
0.021276596
RAB20
0.021276596
RANBP9
0.021276596
RC3H2
0.021276596
RETNLB
0
RHCE
0
RNF214
0.021276596
RRP1B
0.021276596
SPATA6
0
SPATS1
0
SSPN
0
SUFU
0.021276596
SPAG4L
0
SYCP1
0
THOC5
0.021276596
TRIM56
0.021276596
TRIM62
0.021276596
TUBB2C
0.021276596
UBXN4
0.021276596
VAC14
0.021276596
VRK3
0.021276596
WAC
0.021276596
WDR55
0.021276596
WFDC9
0
ZBTB37
0.021276596
ZCCHC2
0.021276596
ZFP42
0
ZNF135
0
ZNF598
0.021276596,
r i is the counts for probe set i for gene i on the first reference set of probe sets, and g i is the counts for probe set i for gene i on the second reference set of probe sets, the mathematical terms with r i and g i being equal to zero if no digital gene expression data is obtained from a first and second reference set of probe sets;
(e) classifying the subject as belonging to one of the following groups based on the predictor score of (d): (i) ABC DLBCL, (ii) GCB DLBCL, (iii) PMBL, (iv) BL, or (v) MCL,
using the formula:
Submodel
call
=
{
-
1
if
∑
i
y
i
w
i
≤
Lower
cutpoint
0
Lower
cutpoint
<
∑
i
y
i
w
i
<
Upper
cutpoint
1
∑
i
y
i
w
i
≥
Upper
cutpoint
wherein y i is the predictor score, w i are the weights associated with the probe set for each gene as listed below:
ABC/GCB
BL non-Myc
BL myc
PMBL
MCL
Gene
weights
weights
weights
weights
weights
ACPP
0
0
0
0
0
ACTG2
0
0
0
0
0
ADAM12
0
0
0
−2.166433184
0
ADAM28
0
0
0
0
0
ADH1B
0
0
0
0
0
ADIPOO
0
0
0
0
0
ADO
0
0
0
0
0
AHR
0
0
−4.866117918
0
0
AICDA
0
0
0
0
0
AKAP2
0
0
0
19.33144328
0
AKR1C2
0
0
0
0
0
ALOX5
−11.14191131
0
0
0
59.14375571
AMIGO2
0
0
0
0
0
ANKRD13A
−13.1144441
0
0
0
0
ANLN
0
0
0
0
0
ANO3
0
0
0
0
0
ANTXR1
0
0
0
−2.443912822
0
ANUBL1
0
0
0
0
0
APOL1
0
0
0
0
0
ARID3A
16.99118469
0
0
0
0
ARID3B
12.66080868
0
0
0
0
ARID5A
0
0
0
0
0
ARL6IP1
0
0
0
0
0
ARNT2
0
0
0
0
0
ARNTL
0
0
0
0
0
ASB13
−19.64578147
0
0
0
0
ASPM
0
0
0
0
0
ATF3
0
0
0
0
0
ATM
0
0
0
0
0
ATP6V0E1
0
0
0
0
0
AUH
0
0
0
20.46302485
0
AURKA
0
0
0
0
0
AUTS2
−15.20513307
0
0
0
0
BANK1
0
0
0
−24.53325693
0
BASP1
0
0
0
0
0
BATF
17.98245577
0
0
0
0
BATF3
0
0
0
0
0
BCAT1
0
0
0
0
−74.11099391
BCL10
0
0
0
0
0
BCL2
0
0
0
0
0
BCL2
0
0
0
0
0
BCL2
0
0
0
0
0
BCL2
0
0
0
0
0
BCL2
14.07216258
0
0
0
0
BCL2
0
0
0
0
0
BCL2A1
0
0
−5.947560928
0
0
BCL2L10
9.91380548
0
0
0
0
BCL6
−17.29479012
0
−5.383296889
0
0
BEST3
0
0
0
0
0
BIRC2
0
0
0
0
0
BIRC3
0
0
−5.663158028
0
0
BRC5
0
0
0
0
0
BMP7
0
0
0
0
0
BPGM
0
0
0
0
0
BPNT1
−11.94204992
0
0
0
0
BSPRY
12.55890968
0
0
0
0
BST2
0
0
0
0
0
BTBD19
0
0
0
0
0
BTG1
0
0
0
0
0
BTG2
0
0
0
0
0
BTK
0
0
0
0
0
BUB1
0
0
0
0
0
BUB1B
0
0.129449175
−6.543666003
0
0
C10orf18
−11.23438924
0
0
0
0
C13orf18
14.60869443
0
6.676459404
0
0
C15orf41
0
0
0
0
0
C3orf37
−13.2892376
0
0
0
0
C5AR1
0
0
0
0
0
C5orf41
0
0
0
0
0
C7orf68
0
0
0
0
0
CACNA1D
0
0
0
0
0
CALD1
0
0
0
−2.249574505
0
CAMK2B
0
0
0
0
0
CARD11
13.81862222
0
0
−18.72040556
0
CAV1
0
0
0
0
0
CAV2
0
0
0
0
0
CCDC50
18.68358953
0
5.320661402
0
68.6051667
CCDC75
0
0
0
0
0
CCL17
0
0
0
25.50999568
0
CCNA2
0
0
0
0
0
CCNB1
0
0
0
0
0
CCNB2
0
0
0
0
0
CCND1
0
0
0
0
0
CCND1
0
0
0
0
0
CCND1
0
0
0
0
0
CCND1
0
0
0
0
0
CCND1
0
0
0
0
0
CCND1
0
0
0
0
87.99680321
CCND2
13.55862157
0
0
0
0
CCND3
0
0
0
0
0
CCR7
11.22811168
0
−4.862612697
0
0
CD2
0
0
0
0
0
CD200
0
0
0
0
0
CD22
0
0
0
0
0
CD247
0
0
0
0
0
CD274
0
0
0
0
0
CD3D
0
0
0
0
0
CD3E
0
0
0
0
0
CD3G
0
0
0
0
0
CD40
0
0
0
0
0
CD44
13.50378135
0
−5.782231847
0
0
CD47
0
0
0
0
0
CD5
0
0
0
0
0
CD58
0
0
0
0
0
CD6
0
0
0
0
0
CD74
0
0
0
0
0
CD79A
0
0
0
0
0
CD79B
0
0
0
0
0
CD8A
0
0
0
0
0
CD8B
0
0
0
0
0
CDC20
0
0
0
0
0
CDC25B
0
0
0
0
0
CDC25C
0
0
0
0
0
CDCA3
0
0
0
0
0
CDCA5
0
0
0
0
0
CDCA8
0
0
0
0
0
CDH11
0
0
0
−2.338738276
0
CDC2
0
0
0
0
0
PFTK1
−15.92270263
0
0
0
0
CDK4
0
0
0
0
0
CDK6
0
0
0
0
−65.86959926
CDKN2A
0
0
0
0
0
CDKN2A
0
0
0
0
0
CDKN3
0
0
0
0
0
CELSR1
0
0
0
0
0
CENPA
0
0
0
0
0
CENPE
0
0
0
0
0
CENPF
0
0
0
0
0
CENPN
0
0
0
0
0
PRR6
0
0
0
22.43680643
0
CEP55
0
0
0
0
0
CFLAR
16.61287119
0
−5.100315997
0
0
CGNL1
0
0
0
−2.156504887
0
CIITA
0
0
0
0
0
CKS2
0
0
0
0
0
CLIP2
0
0
0
20.2768953
0
CLMN
0
0
0
0
0
CPNE3
−11.49752906
0
0
0
0
CR2
−12.2225611
0
−5.465732584
−19.63179827
0
CREB3L2
19.29029329
0
0
0
0
CREBBP
0
0
0
0
0
CSF2RA
0
0
0
−2.424880636
0
CSTA
0
0
0
−2.543864326
0
CTGF
0
0
0
0
0
CTH
0
0
0
0
0
CTHRC1
0
0
0
−2.518684898
0
CTLA4
0
0
0
0
0
CTNNA2
0
0
0
0
0
CTPS
0
0
0
0
0
CTSH
0
0
−5.145507824
0
0
CTSK
0
0
0
−2.572873829
0
CXCL10
0
0
0
0
0
CXCL12
0
0
0
0
0
CXCL9
0
0
0
0
0
CYB5R2
19.12600362
0
0
0
0
CYP27A1
0
0
0
−2.635085165
0
CYP2J2
0
0
0
0
0
CYSLTR1
0
0
0
0
0
DCBLD1
0
0
0
0
0
DCTD
15.98936135
0
0
0
0
DDAH2
0
0
0
0
0
DDX58
0
0
0
0
0
DENND4A
0
0
0
21.20254474
0
DLC1
0
0
0
0
0
DLEU1
0
0
0
0
0
DLGAP5
0
0
0
0
0
DNAJA1
0
0
0
0
0
DNAJB9
0
0
0
0
0
DNAJC10
−12.209423
0
0
0
0
DNMT3A
0
0
0
0
0
DOCK10
15.87228876
0
0
17.13938941
0
DPY19L1
0
0
0
0
0
DPYSL3
0
0
0
−2.427210322
0
DRAM
0
0
0
0
0
DTX1
0
0
0
0
0
E2F2
0
0
4.871853059
0
0
E2F8
0
0
0
0
0
EBV_BZLF1
0
0
0
0
0
EBV_EBER1
0
0
0
0
0
EBV_EBER2
0
0
0
0
0
EBV_EBNA1_CDS
0
0
0
0
0
EBV_EBNA2_3′_end
0
0
0
0
0
EBV_EBNA2_long
0
0
0
0
0
EBV_EBNA3A
0
0
0
0
0
EBV_EBNA3B
0
0
0
0
0
EBV_EBNA3C
0
0
0
0
0
EBV_LMP1_3′_end
0
0
0
0
0
EBV_LMP1_unique
0
0
0
0
0
EBV_LPM2A
0
0
0
0
0
EEPD1
−14.43898719
0
0
0
0
EFEMP2
0
0
0
−2.309390981
0
EGFL7
0
0
0
0
0
EHD2
0
0
0
0
0
EIF5AL1
0
0
0
0
0
ELL2
12.74051826
0
−5.784944094
0
0
EML1
0
0
0
−2.370584039
0
EMR1
0
0
0
0
0
ENO1
0
0
0
0
0
ENPP3
0
0
0
0
0
ENTPD1
12.50562718
0
0
0
0
EP300
0
0
0
0
0
EPHB1
0
0
0
0
0
EPSTII
0
0
0
0
0
ERG
0
0
0
0
0
ERP29
14.40630514
0
0
0
0
TXNDC4
0
0
0
0
0
ESPL1
0
0
0
0
0
ETV6
17.10124803
0
0
0
0
EXO1
0
0
0
0
0
FABP4
0
0
0
0
0
FAM108C1
13.9119712
0
0
0
0
FAM159A
0
0
0
−19.09112771
0
FAM171B
0
0
0
20.15840479
0
FAM46C
16.04589049
0
0
0
0
FAM69A
0
0
0
20.26920874
0
FAM83D
0
0
0
0
0
FAP
0
0
0
−2.448537997
0
FAS
0
0
0
19.4917463
0
FBP2
0
0
0
0
0
FBXO10
0
0
0
0
0
FBXO11
0
0
0
0
0
FCER2
0
0
0
19.36530173
0
FEZ1
0
0
0
0
0
FGL2
0
0
0
0
0
FKBP11
10.77110305
0
0
0
0
FKBP2
0
0
0
0
0
FLJ42418
−13.07282539
0
0
0
0
FLNA
0
0
0
0
0
FN1
0
0
0
−2.515692387
0
FNBP1
0
0
0
0
0
FNDC1
−9.924277783
0
0
−2.337279029
0
FOXM1
0
0
0
0
0
FOXO1
0
0
0
0
0
FOXP1
0
0
0
0
0
FSCN1
0
0
0
0
0
FUT8
12.89311878
0
0
0
0
FYB
0
0
0
0
0
GBP1
0
0
0
0
0
GBP4
0
0
0
0
0
GCET2
0
0
0
17.14715594
0
GGT1
0
0
0
0
0
GHR
0
0
0
0
0
GLDC
0
0
0
0
0
GLRX
0
0
0
0
0
GNA13
−13.98237394
0
0
0
0
GNB4
0
0
0
0
0
GNG10
0
0
0
0
0
GNL3
13.0455436
0.131002027
−6.622162805
0
0
GPR116
0
0
0
0
0
GPR176
0
0
0
0
0
GPR183
0
0
0
0
0
GRAMD1B
0
0
0
0
0
GRB10
0
0
0
0
0
GRSF1
0
0
0
0
0
GTSE1
0
0
0
0
0
GLT8D4
0
0
0
0
0
GYPC
0
0
0
17.83003931
0
H2AFV
0
0
0
0
0
H2AFX
0
0
0
0
0
HCK
15.54344514
0
−5.412764958
0
0
HDAC1
−15.02975702
0
0
0
0
HDAC2
0
0
0
0
0
HDGF
0
0.116000721
−5.863845581
0
0
HEG1
0
0
0
−2.46106726
0
HHV8_BCL2_homologue
0
0
0
0
0
HHV8_K1-32_Bcb_K
0
0
0
0
0
1_protein
HHV8_ORF7
0
0
0
0
0
3-LANA
HHV8_T0.7/P6
0
0
0
0
0
HHV8_T1.1
0
0
0
0
0
HHV8_vFLIP_ORF71
0
0
0
0
0
HHV8_vIL6
0
0
0
0
0
HHV8_vMIP1b_
0
0
0
0
0
ORFK4.2_KIE-3
HJURP
0
0
0
0
0
HLA-A
0
0
0
0
0
HLA-B
0
0
0
0
0
HLA-C
0
0
0
0
0
HLA-DMA
0
0
−4.825417012
0
0
HLA-DPA1
0
0
0
0
0
HLA-DPB1
0
0
0
0
0
HLA-DQA1
0
0
0
0
0
HLA-DRA
0
0
0
0
0
HLA-E
0
0
0
0
0
HLA-F
0
0
0
0
0
HOMER2
0
0
0
19.38721241
0
HOPX
−14.01730842
0
0
0
0
HPCAL1
0
0
0
0
59.25326244
HSP90B1
15.53130763
0
0
0
0
HSPB8
0
0
0
−2.192325405
0
HTRA1
0
0
0
−2.354416381
0
HYOU1
0
0
0
0
0
ICAM1
0
0
−5.307124944
0
0
ID1
0
0
0
0
0
ID2
0
0
0
0
0
ID3
0
0
0
0
0
IDS
0
0
0
0
0
IER3
0
0
0
0
0
IFI16
0
0
0
0
0
IFI35
0
0
0
0
0
IFI44L
0
0
0
0
0
IFI6
0
0
0
0
0
IFIH1
0
0
0
21.31413442
0
IFIT1
0
0
0
0
0
IFIT2
0
0
0
0
0
IFIT3
0
0
0
0
0
IFITM1
0
0
0
0
0
IFNAR1
0
0
0
0
0
IFNAR2
0
0
0
0
0
IFNB1
0
0
0
0
0
IgA2_constant_region
0
0
0
0
0
IgE_constant_region
0
0
0
0
0
IGSF3
0
0
0
0
0
IgG2_constant_region
0
0
0
0
0
IgG4_constant_region
0
0
0
0
0
IGSF3
11.04304441
0
0
18.36718646
0
IL10
0
0
0
0
0
IL12A
10.87451224
0
0
0
0
IL13
0
0
0
0
0
IL13RA1
0
0
0
22.21511102
0
IL16
15.38015948
0
0
0
0
IL17RB
10.16999574
0
0
0
0
IL4I1
0
0
0
0
0
IL6
0
0
0
0
0
ING1
0
0
0
0
0
INPP5D
0
0
0
0
0
IRAK1
0
0
0
0
0
IRAK2
0
0
0
0
0
IRAK3
0
0
0
0
0
IRAK4
0
0
0
0
0
IRF1
0
0
0
0
0
IRF3
0
0
0
0
0
IRF4
21.21696785
0
0
0
0
IRF5
0
0
0
0
0
IRF7
0
0
0
0
0
ISG15
0
0
0
18.22975543
0
ITGA9
0
0
0
0
0
ITGAV
0
0
0
−2.502427838
0
ITGAX
0
0
0
−2.527107115
0
ITGB2
0
0
−5.354319759
0
0
ITPKB
−19.39129721
0
0
0
0
JAK1
0
0
0
0
0
JAK2
0
0
0
18.78741327
0
JAK3
0
0
−4.911758111
12
0
KCNJ1
0
0
0
0
0
KCNK12
−12.19178395
0
0
0
0
KCNMA1
0
0
0
0
0
JMJD2C
0
0
0
0
0
KDR
0
0
0
0
0
KIAA1147
0
0
0
0
0
K1AA1274
−11.88673995
0
0
0
0
KIF11
0
0
0
0
0
KIF14
0
0
0
0
0
KIF15
0
0
0
0
0
KIF18A
0
0
0
0
0
KIF18B
0
0
0
0
0
KIF20A
0
0
0
0
0
KIF23
0
0
0
0
0
KIF2C
0
0
0
0
0
KIF4A
0
0
0
0
0
KLHL5
−10.77233553
0
0
0
0
KPNA2
0
0
0
0
0
KYNU
0
0
0
23.67824397
0
LAMB1
0
0
0
0
0
LAMP3
0
0
0
0
0
LANCL1
−11.96529389
0
0
0
0
LAT
0
0
0
0
0
LAT2
0
0
0
0
0
LDHA
0
0
0
0
−62.43798035
LHFPL3
0
0
0
0
0
LHX2
0
0
0
0
0
LIMA1
0
0
0
22.38509346
0
LIMD1
17.83248768
0
0
0
0
LMAN2
0
0
0
0
0
LMO2
−16.98695863
0
−9.427107802
0
0
LOC643529
0
0
0
0
0
LOXL2
0
0
0
0
0
LPCAT3
0
0
0
0
0
LRMP
−15.8755653
0
0
0
0
LRPPRC
0
0
0
0
0
LRRC15
−12.69088474
0
0
−2.555292482
0
LRRC33
15.08028382
0
0
0
0
LTBP2
0
0
0
−2.274436223
0
LYPD6B
−12.18942045
0
0
0
0
LYZ
0
0
0
−2.548310761
0
MACROD2
0
0
0
0
0
MAL
0
0
0
21.94306064
0
MALT1
0
0
0
0
0
MAML3
−17.94799886
0
0
0
0
MAP3K1
0
0
0
0
55.17626389
MAP3K8
0
0
0
0
0
MAP4K4
−10.29136026
0
0
0
0
MAPK10
−14.19048558
0
0
0
0
MAPKAPK5
0
0
0
0
0
MARCKS
0
0
0
0
0
MARCKSL1
−16.15992041
0
−5.183663919
0
0
MAST2
−13.37445723
0
0
0
0
MATR3
0
0
0
0
0
MCL1
0
0
0
0
0
MCM10
0
0
0
0
0
MCM7
0
0
0
0
0
MDFIC
0
0
−6.830814658
0
0
MDM2
0
0
0
0
0
MFAP5
0
0
0
0
0
MFNG
0
0
0
0
0
MFSD2A
0
0
0
0
0
MGC87042
0
0
0
0
0
MIR17HG
0
0
0
0
0
MKI67
0
0
0
0
0
MME
−18.26084621
0
0
0
0
MMP1
0
0
0
0
0
MMP2
0
0
0
−2.575770684
0
MMP9
0
0
0
−2.62062289
0
MMRN2
0
0
0
0
0
MNDA
0
0
0
0
0
MOBKL2C
0
0
0
24.05195347
0
MPEG1
13.61757622
0
0
0
0
MS4A1
0
0
0
0
0
MST1R
0
0
0
0
0
MTHFD2
0
0
0
0
−64.88192756
MUC16
0
0
0
0
0
MYB
0
0
6.206314452
0
0
MYBL1
−19.42564163
0
0
0
0
MYC
0
0.129410593
−6.541715697
0
0
MYD88
0
0
0
0
0
MYO7A
0
0
0
0
0
FAM128B
0
0
0
0
0
NANS
0
0
−5.411187191
0
−62.00052085
NASP
0
0
0
0
0
NBN
0
0
0
0
0
NCAPG
0
0
0
0
0
NCAPH
0
0
0
0
0
NCF2
0
0
0
17.12736383
0
NCRNA00158
0
0
0
0
0
NDST4
0
0
0
0
0
NECAP2
0
0
0
17.90953211
0
NEIL1
−16.14074081
0
0
0
0
NEK6
−14.536944
0
0
0
0
NFATC1
0
0
0
0
0
NFIL3
0
0
0
23.55828096
0
NFKBIA
0
0
0
0
0
NFKBIZ
14.96909754
0
0
0
0
NIPA2
12.59506241
0
0
0
0
NOC3L
11.52493513
0
0
0
0
NOL14
0
0
0
0
0
NOL5A
0
0.123010002
−6.218165306
0
0
NOTCH1
0
0
0
0
0
NOTCH2
0
0
0
0
0
NUF2
0
0
0
0
0
NUP62
0
0
0
0
0
NUSAP1
0
0
0
0
0
OAS2
0
0
0
0
0
OAS3
0
0
0
0
0
OPN3
0
0
0
0
0
OSBPL3
−13.37500509
0
0
0
0
PA2G4
0
0
0
0
0
PAG1
−16.35818989
0
0
0
0
DKEZP564O0823
0
0
0
0
0
PAX6
0
0
0
0
0
PCNA
0
0
0
0
0
PDCD1LG2
0
0
0
0
0
PDE9A
−12.58569832
0
0
0
0
PDGFRA
0
0
0
0
0
PDIA4
0
0
0
0
0
PDIA5
11.45635103
0
0
0
0
PDK4
0
0
0
0
0
PDLIM1
14.15712166
0
0
0
0
PDLIM3
0
0
0
0
0
PDPN
0
0
0
−2.469335735
0
PECAM1
0
0
0
0
0
PECR
0
0
0
0
0
PGAM1
0
0
0
0
0
PHC3
0
0
0
0
0
PHF16
15.59828263
0
0
0
0
PIK3CA
0
0
0
0
0
PIK3CD
0
0
0
0
0
PIM1
13.17752239
0
0
0
0
PIM2
19.17848124
0
0
0
0
PLAU
0
0
−4.942137646
−2.638406534
0
PLEK
0
0
−5.140753466
0
0
PLEKHF2
−14.32290025
0
0
0
0
PLEKHG4B
0
0
0
0
0
PLXNB1
0
0
0
0
0
PMEPA1
−11.10781933
0
0
−2.5144432
0
PMP22
0
0
0
0
0
NP
11.18914667
0
0
0
0
POU2AF1
0
0
0
0
0
POU2F1
0
0
0
0
0
POU2F2
0
0
0
0
0
PPA1
0
0
0
0
−58.07910524
PPP2R3B
0
0
0
0
0
FAM152B
0
0
0
0
0
PRDM1
0
0
0
0
0
PRDM12
0
0
0
0
0
PRDX2
0
0
0
−23.58686384
0
PRDX4
0
0
0
0
0
PRICKLE1
0
0
0
0
56.2707098
PRKCB
0
0
0
−16.97009784
0
PRMT1
0
0
0
0
0
PRPSAP2
−12.13413417
0
0
0
0
PRSS1
0
0
0
0
0
PSMG1
0
0
0
0
0
PTEN
0
0
0
0
0
PTGER4
0
0
0
0
0
PTGIR
0
0
0
26.72740141
0
PTK2
−13.78968685
0
−4.948036735
0
0
PTPN1
13.38225581
0
0
0
0
PTPRB
0
0
0
0
0
PVRL1
0
0
0
0
0
PXDN
0
0
0
0
0
OSOX1
0
0
0
0
0
RAB31
0
0
0
0
0
RAB33A
0
0
−4.912839787
0
0
RAB3A
0
0
0
0
0
RAB7L1
20.66492996
0
0
0
0
RAPGEF5
−14.68045686
0
0
0
0
RARRES2
0
0
0
−2.570678175
0
RASGRP3
0
0
−6.000117265
0
0
RASSF4
0
0
0
0
0
RBCK1
0
0
0
0
0
RCL1
0
0
0
19.91410729
0
REL
−10.88675527
0
0
0
0
RFTN1
−10.08136072
0
0
0
0
RGL1
0
0
0
0
0
RGS9
0
0
0
18.38318043
0
RHEBL1
0
0
0
0
0
RHOF
0
0
0
19.45176982
0
RHOXF1
0
0
0
0
0
RNASEH2B
0
0
0
0
0
RNF31
0
0
0
0
0
RNGTT
0
0
0
0
0
ROBO1
0
0
0
−2.163573921
ROBO4
0
0
0
0
0
RPN2
0
0
0
0
0
RPS6KA5
0
0
0
0
0
RSAD2
0
0
0
0
0
RTCD1
0
0
0
0
0
RUNDC2B
0
0
0
0
0
RXRA
0
0
0
0
0
S100Z
−12.22316337
0
0
0
0
S1PR2
−21.44566507
0
0
0
0
SAA1
0
0
0
0
0
SACS
12.97435391
0
0
0
0
SAE1
0
0
0
0
0
SAMSN1
0
0
−5.803971429
22.68315196
0
SAP30
0
0
0
0
0
SCARA5
0
0
0
−2.335496267
0
SDC1
0
0
0
0
0
SDCCAG8
0
0
0
0
0
KIAA0746
−15.04224714
0
0
0
0
SEMA7A
0
0
0
0
0
SEPHS1
0
0
0
0
0
SERBP
0
0
0
0
0
SERPINA9
−17.70615386
0
−4.937282176
0
0
SERPINB1
0
0
0
0
0
SFN
0
0
0
0
0
SFPQ1
0
0
0
0
0
SGK1
−9.835329752
−5.684745402
0
0
SGOL2
0
0
0
0
0
SH2D1A
0
0
0
0
0
SH3BP5
17.2475192
0
0
0
0
SHARPIN
0
0
0
0
0
SIDT1
10.70030882
0
0
0
0
SIRPA
0
0
0
0
0
SIRPB1
0
0
0
0
0
SLA
16.00267223
0
0
0
0
SLAMF1
−13.70193031
0
−5.135970135
20.7055292
0
SLC12A8
0
0
0
0
0
SLC16A9
0
0
0
0
0
SLC1A4
0
0
0
0
0
SLC31A1
0
0
0
0
0
SLC35E2B
0
0
0
0
0
SLC38A5
16.76798547
0
0
0
0
SMAD1
0
0
0
0
0
SMAD7
0
0
0
0
0
SMARCA4
−13.90289239
0
5.037186022
0
0
SNAP23
0
0
0
0
0
SNN
0
0
0
0
67.01976847
SNX11
0
0
0
22.05768278
0
SNX22
−13.10658722
0
0
0
0
SNX29
0
0
0
19.13395502
0
SOCS1
0
0
0
0
0
SOCS2
0
0
0
0
0
SOCS3
0
0
0
0
0
SORBS1
0
0
0
0
0
SOX11
0
0
0
0
54.39896926
SOX5
0
0
0
0
0
SPAG5
0
0
0
0
0
SPARC
0
0
0
−2.470075697
0
SPARCL1
0
0
0
0
0
SPIB
0
0
0
0
0
SPINK2
−10.030466
0
0
0
0
SPINT2
0
0
0
19.59153543
0
SPON1
0
0
0
0
0
SPRED2
−11.78392433
0
0
0
0
SPRY1
0
0
0
0
0
SRPK1
0
0
0
0
0
SRPX
0
0
0
0
0
SRSF1
0
0
0
0
0
SSBP2
−16.54355885
0
0
0
0
STAG3
0
0
0
0
0
STAMBPL1
14.49186031
0
0
0
0
STAP1
−12.71264348
0
0
0
0
STAT1
0
0
0
0
0
STAT3
10.99589419
0
−5.30437752
0
0
STEAP1
0
0
0
0
0
STK17A
−12.60874641
0
0
0
0
STK38L
0
0
0
0
0
STMN1
0
0
0
0
0
STS
−9.978596163
0
0
0
0
STX11
0
0
−5.423455974
0
0
SULF1
0
0
0
−2.512044172
0
SYK
0
0
0
0
0
SYPL1
0
0
0
0
0
SYT17
0
0
0
0
0
SYTL4
0
0
0
0
0
TARS
13.55653507
0
0
0
0
TAXIBP1
0
0
0
0
0
TBC1D27
0
0
0
0
0
TBC1D9
0
0
0
0
61.55561013
TCF3
0
0
5.046896623
0
0
TCF4
15.61877166
0
0
0
0
TCTN3
13.00379932
0
0
0
0
TEAD1
0
0
0
0
0
TEK
0
0
0
0
0
TERT
0
0.125565268
−6.347334222
0
0
TEX9
−12.41661821
0
0
0
0
TFDP2
0
0
0
0
0
TFPI2
0
0
0
0
0
TGFBR1
0
0
0
0
0
THBS2
0
0
0
−2.458163143
0
THY1
0
0
0
−2.435821946
0
TIAM2
−10.50158544
0
0
0
0
TICAM2
10.36653445
0
−4.996251154
0
0
TJP2
0
0
0
0
0
TK1
0
0
0
0
0
TLE4
0
0
0
17.47264051
0
TLK1
12.28505922
0
0
0
0
TLR7
0
0
0
19.4679966
0
TM4SF1
0
0
0
0
0
TMBIM6
0
0
0
0
0
TMEM109
0
0
0
0
0
TMEM119
−10.5658305
0
−5.379086543
−2.658347176
0
TMOD1
0
0
0
19.102924
0
TMPRSS6
0
0
0
0
0
TNF
0
0
0
0
0
TNFAIP2
0
0
0
0
0
TNFAIP3
0
0
0
0
0
TNFRSF13B
19.52210849
0
0
0
0
TNFRSF14
0
0
0
0
0
TNFRSF17
0
0
0
20.07405253
0
TNFRSF19
0
0
0
0
0
TNFSF10
0
0
0
0
0
TNFSF4
0
0
0
27.41538607
0
TNIP2
0
0
0
0
0
TNXB
0
0
0
0
0
TOP2A
0
0
0
0
0
TOX
−11.9192864
0
0
0
0
TP53
0
0
0
0
0
TP73
0
0
0
0
0
TPM1
0
0
0
−2.197810042
0
TPX2
0
0
0
0
0
TRAF1
0
0
0
21.57006782
0
TRAF3
0
0
0
0
0
TRIM25
0
0
0
0
0
TRIM6-TRIM34
0
0
0
0
0
TRIP13
0
0.122871716
−6.211174921
0
0
TTC9
−12.56263701
0
0
0
0
TUBG1
0
0
0
0
0
TXN
0
0
0
0
0
TXNDC5
0
0
0
0
0
TYK2
0
0
0
0
0
TYMS
0
0
0
0
0
UBE2I
0
0
0
0
0
UBE2S
0
0
0
0
0
USP12
−11.66057366
0
0
0
0
USP18
0
0
0
0
0
USP46
13.42760916
0
0
0
0
VASH2
0
0
0
20.35631229
0
VGLL4
12.24069542
0
0
0
0
TMEM49
0
0
0
0
0
VWF
0
0
0
0
0
WASF1
0
0
0
0
0
WDR25
0
0
0
0
0
WHSC1
0
0
0
0
0
WNT3
0
0
0
0
55.5970345
XAF1
0
0
0
0
0
XBP1
10.72031521
0
0
0
0
YPEL1
0
0
0
0
0
ZAP70
0
0
0
0
0
ZBTB32
12.89819312
0
0
0
0
ZBTB38
0
0
0
0
0
ZBTB8
0
0
0
22.31265521
0
ZCCHC7
−10.53054134
0
0
0
0
ZFP36L1
0
0
0
0
0
ZMYND8
0
0
0
0
0
ZNF238
0
0
0
0
0
ZNF281
0
0
0
17.18038245
0
ZNF318
−14.69750421
0
0
0
0
ZNF385B
0
0
0
0
0
ZNF608
−12.02764268
0
0
0
0
ZNRF1
0
0
0
0
0
ZPBP2
0
0
0
0
0
ZWINT
0
0
0
0
0
A2LD1
0
0
0
0
0
ABCA12
0
0
0
0
0
ACSL5
0
0
0
0
0
AHCYL2
0
0
0
0
0
AKAP9
0
0
0
0
0
ASCL2
0
0
0
0
0
ASMTL-AS1
0
0
0
0
0
ATOH8
0
0
0
0
0
ATXN7L2
0
0
0
0
0
C19orf26
0
0
0
0
0
C4orf31
0
0
0
0
0
CA7
0
0
0
0
0
CAMKK1
0
0
0
0
0
CDK5RAP2
0
0
0
0
0
CHD4
0
0
0
0
0
CHST5
0
0
0
0
0
CPA6
−10.24419002
0
0
0
0
DAZAP2
0
0
0
0
0
DCLK3
0
0
0
0
0
DNAJB12
0
0
0
0
0
ERBB2IP
0
0
0
0
0
ERN2
0
0
0
0
0
KIAA0574
0
0
0
0
0
FAR2
0
0
0
0
0
FARP1
0
0
0
0
0
FBXL13
0
0
0
0
0
FBXO36
0
0
0
0
0
FBXO41
0
0
0
0
0
FCN2
0
0
0
0
0
GAD2
0
0
0
0
0
GATA1
0
0
0
0
0
GATA2
0
0
0
0
0
GIT2
0
0
0
0
0
GNG4
0
0
0
0
0
GORASP1
0
0
0
0
0
GSK3B
0
0
0
0
0
GYG2
0
0
0
0
0
H1FOO
0
0
0
0
0
HARBI1
0
0
0
0
0
HHIP
0
0
0
0
0
HSP90AA1
0
0
0
0
0
HSPA12B
0
0
0
0
0
HSPA9
0
0
0
0
0
IK
0
0
0
0
0
ISY1
0
0
0
0
0
KCNQ3
0
0
0
0
0
KCP
0
0
0
0
0
KIF6
0
0
0
0
0
KRAS
0
0
0
0
0
LRP3
0
0
0
0
0
MLL2
0
0
0
0
0
MLLT10
0
0
0
0
0
MSX2
0
0
0
0
0
KIAA0774
0
0
0
0
0
NAIF1
0
0
0
0
0
NEBL
0
0
0
0
0
NEU3
0
0
0
0
0
NHLH2
0
0
0
0
0
NRG1
0
0
0
0
0
OPA1
0
0
0
0
0
PDE4DIP
0
0
0
0
0
RNUXA
0
0
0
0
0
PHF23
0
0
0
0
0
PMCHL1
0
0
0
0
0
PNLIP
0
0
0
0
0
PPP3CC
0
0
0
0
0
PTENP1
0
0
0
0
0
PTPN21
0
0
0
0
0
PTRH1
0
0
0
0
0
R3HDM1
0
0
0
0
0
RAB20
0
0
0
0
0
RANBP9
0
0
0
0
0
RC3H2
0
0
0
0
0
RETNLB
0
0
0
0
0
RHCE
0
0
0
0
0
RNF214
0
0
0
0
0
RRP1B
0
0
0
0
0
SPATA6
0
0
0
0
0
SPATS1
0
0
0
0
0
SSPN
0
0
0
0
0
SUFU
0
0
0
0
0
SPAG4L
0
0
0
0
0
SYCP1
0
0
0
0
0
THOC5
0
0
0
0
0
TRIM56
0
0
0
0
0
TRIM62
0
0
0
0
0
TUBB2C
0
0
0
0
0
UBXN4
0
0
0
0
0
VAC14
0
0
0
0
0
VRK3
0
0
0
0
0
WAC
0
0
0
0
0
WDR55
0
0
0
0
0
WFDC9
0
0
0
0
0
ZBTB37
0
0
0
0
0
ZCCHC2
0
0
0
0
0
ZFP42
0
0
0
0
0
ZNF135
0
0
0
0
0
ZNF598
0
0
0
0
0,
and the upper and lower cutpoints for ABC/GCB, BL non-myc, BL myc, PMBL, and MCL submodels are as listed for each submodel below:
Submodel
Lower Cut-point
Upper Cut-point
ABC/GCB
712.91
1238.61
BL Non-Myc
−89.39
−60.39
BL Myc
1.11
1.11
PMBL
−400.06
−150.06
MCL
−51.92
359.08,
and using the logic:
(1) if the MCL submodel has a value of 1, the sample is called MCL,
if the MCL submodel has a value of 0, the sample is called unclassifiable but borderline MCL,
if the MCL submodel has a value of −1, proceed to step 2,
(2) if the BL non-myc submodel has a value of 1, proceed to step 3,
if the BL non-myc submodel has a value of 0, the sample is called unclassifiable but borderline BL,
if the BL non-myc submodel has a value of −1, proceed to step 4,
(3) if the BL myc submodel has a value of 0 or 1, the sample is called BL,
if the BL myc submodel has a value of −1, the sample is called unclassifiable but borderline BL,
(4) if the PMBL submodel has a value of 1, the sample is called PMBL,
if the PMBL submodel has a value of 0, the sample is called unclassifiable but borderline PMBL,
if the PMBL submodel has a value of −1, proceed to step 5,
(5) if the ABC/GCB submodel has a value of 1, the sample is called ABC,
if the ABC/GCB submodel has a value of 0, the sample is called unclassified DLBCL,
if the ABC/GCB submodel has a value of −1, the sample is called GCB; and
(f) providing treatment to the subject, wherein the treatment is (i) R-CHOP or ibrutinib if the classification of (e) is GCB DLBCL, (ii) ibrutinib if the classification of (e) is ABC DLBCL, (iii) CHOP, ibrutinib, immunotherapy, radioimmunotherapy, protoesome inhibitors, or mTor inhibitors if the classification of (e) is MCL, (iv) R-EPOCH, ibrutinib, CODOX-M/IVAC therapy, immunotherapy, bone marrow transplantation, stem cell transplantation, surgery, or radiotherapy if the classification of (e) is BL, or (v) R-CHOP, ibrutinib, high-dose chemotherapy, radiotherapy, or stem cell transplantation if the classification of (e) is PMBL.
2. The method of claim 1 , wherein the gene expression product is isolated from a formalin-fixed and paraffin-embedded (FFPE) biopsy sample from the subject.
3. The method of claim 2 , wherein the digital gene expression data is obtained using an assay comprising color-coded probes.