Table 1

Characteristics of the 70 variants identified by targeted deep sequencing of TCR, JAK/STAT, and TLR-related genes in 85 TFH-derived PTCL samples

Functional groupsGeneAmino acid changeMutation typeDomainNew/reportedEffectReferences
Costimulatory and proximal TCR signaling CD28 D124V Missense Extracellular AITL, ATLL Gain of function (F) 20,25  
CD28 D124E Missense Extracellular AITL, ATLL Gain of function (F) 20,25  
CD28 T195P Missense Cytoplasmic AITL, ATLL Gain of function (F) 20,25,30  
LCK N446K* Missense Kinase New Probably gain of function (P)  
LCK P447R* Missense Kinase New Probably gain of function (P)  
FYN Q527X Stop gain  ATLL Probably gain of function (P) 20  
FYN 525_525del† Frameshift deletion  New Probably gain of function (P)  
FYN S186L† Missense SH2 New Probably gain of function (P)  
FYN K108fs* Frameshift deletion  New Probably loss of function (P)  
FYN E107S* Missense SH3 New Probably loss of function (P)  
NK-kB/NF-AT pathway PLCG1 E47K Missense PH 1 ATLL Gain of function (F) 20  
PLCG1 R48W Missense PH 1 ATLL, SS No effect (F) 20,24  
PLCG1 D342G Missense PI-PLC X-box ATLL, MF Gain of function (F) 20  
PLCG1 S345F† Missense PI-PLC X-box ATL, MF, SS, ATLL Gain of function (F) 20,-22,24  
PLCG1 S520F† Missense PH 2; first part MF, SS, ATLL Gain of function (F) 20,21,24  
PLCG1 E730K Missense SH2 2 New Gain of function (F)  
PLCG1 G869E Missense Near SH3 New Gain of function (F)  
PLCG1 E1163K Missense C2 ATLL, SS Gain of function (F) 20,24  
PLCG1 D1165H Missense C2 ATLL, SS Gain of function (F) 20,24  
PLCG1 D1165G Missense C2 ATLL Gain of function (F) 20  
CARD11 F902C Missense  ATLL Gain of function (F) 20  
CARD11 S547T Missense  New Gain of function (F)  
CARD11 F176C Missense Coiled coil New Gain of function (F)  
TRAF6 Q347X Stop gain Coiled coil /MATH New NA  
PI3K pathway PIK3R1 K141R Missense RHO-GAP New Probably gain of function (P)  
PIK3R1 Q475P Missense iSH2 New Probably gain of function (P)  
PIK3R1 T576A Missense iSH2 New Probably gain of function (P)  
PIK3R1 G680S Missense SH2 2 New Probably gain of function (P)  
PIK3R1 V704M Missense SH2 2 New Probably gain of function (P)  
PIK3R5 A259V Missense  Carcinoma (liver) Probably gain of function (P) 31  
PIK3CA L1001P Missense PI3K/PI4K New Probably gain of function (P)  
PDPK1 19_20del Inframe deletion  New NA  
PDPK1 151_152del Frameshift deletion Protein kinase New Probably loss of function (P)  
PDPK1 R324Q Missense Protein kinase New Probably gain of function (P)  
PDPK1 P340Q Missense Protein kinase New Probably gain of function (P)  
AKT1 G294R Missense Protein kinase New Probably gain of function (P)  
CTNNB1 T41A† Missense Phospho by GSK3b Hepatocellular carcinoma, acute lymphoblastic leukemia, breast cancer, Wilms’ tumor Gain of function (F) 32  
CTNNB1 H36P Missense  Hepatocellular carcinoma, acute lymphoblastic leukemia, breast cancer, Wilms’ tumor Gain of function (F) 32  
CTNNB1 S45F† Missense  Hepatocellular carcinoma, acute lymphoblastic leukemia, breast cancer, Wilms’ tumor Gain of function (F) 32  
CTNNB1 K335T Missense  Hepatocellular carcinoma Gain of function (F) 33  
AP-1/MAPK pathway KRAS I36M Missense  Hematopoeitic neoplasms Gain of function (F) 34  
KRAS A18D Missense GTP binding Lymphoma Gain of function (F) 34  
KRAS G13D Missense GTP binding Solid tumors Gain of function (F) 34  
MAPK3 R278Q Missense Protein kinase New Probably gain of function (P)  
STAT3 E616G Missense SH2 Lymphoma Gain of function (F) 26,35  
STAT3 E616K Missense SH2 Lymphoma Gain of function (F) 26,35  
GTF2I D317E Missense  New Probably gain of function (P)  
GTF2I N340S Missense  New Probably gain of function (P)  
GTF2I R523S Missense GTF2I-like New Probably gain of function (P)  
GTF2I L607F Missense GTF2I-like New Probably gain of function (P)  
GTF2I R702Q Missense  New Probably gain of function (P)  
GTPases pathway RHOA K18N Missense GTP binding New Gain of function (F)  
RHOA G17V Missense GTP binding AITL, ATLL Dominant negative (F) 12,-14,20,36  
VAV1 151_158del Frameshift deletion  New Probably loss of function (P)  
VAV1 778_783del Frameshift deletion  New Probably gain of function (P)  
VAV1 D797G Missense SH3 2 New Probably gain of function (P)  
VAV1 Y826S Missense SH3 2 New Probably gain of function (P)  
VAV2 Y214C Missense DH Gastric carcinoma Probably dominant negative (P)  
JAK/STAT and TLR pathways JAK1 D831E Missense Kinase New Probably gain of function (P)  
JAK2 V617F Missense  Myeloproliferative disorders Gain of function (F) 37,,,,,-43  
JAK3 A699V Missense Kinase Lymphoma, carcinoma Gain of function (F) 37,,,,,-43  
MYD88 S219C Missense TIR DLBCL, lymphocytic leukemia Probably gain of function (P) 44  
Functional groupsGeneAmino acid changeMutation typeDomainNew/reportedEffectReferences
Costimulatory and proximal TCR signaling CD28 D124V Missense Extracellular AITL, ATLL Gain of function (F) 20,25  
CD28 D124E Missense Extracellular AITL, ATLL Gain of function (F) 20,25  
CD28 T195P Missense Cytoplasmic AITL, ATLL Gain of function (F) 20,25,30  
LCK N446K* Missense Kinase New Probably gain of function (P)  
LCK P447R* Missense Kinase New Probably gain of function (P)  
FYN Q527X Stop gain  ATLL Probably gain of function (P) 20  
FYN 525_525del† Frameshift deletion  New Probably gain of function (P)  
FYN S186L† Missense SH2 New Probably gain of function (P)  
FYN K108fs* Frameshift deletion  New Probably loss of function (P)  
FYN E107S* Missense SH3 New Probably loss of function (P)  
NK-kB/NF-AT pathway PLCG1 E47K Missense PH 1 ATLL Gain of function (F) 20  
PLCG1 R48W Missense PH 1 ATLL, SS No effect (F) 20,24  
PLCG1 D342G Missense PI-PLC X-box ATLL, MF Gain of function (F) 20  
PLCG1 S345F† Missense PI-PLC X-box ATL, MF, SS, ATLL Gain of function (F) 20,-22,24  
PLCG1 S520F† Missense PH 2; first part MF, SS, ATLL Gain of function (F) 20,21,24  
PLCG1 E730K Missense SH2 2 New Gain of function (F)  
PLCG1 G869E Missense Near SH3 New Gain of function (F)  
PLCG1 E1163K Missense C2 ATLL, SS Gain of function (F) 20,24  
PLCG1 D1165H Missense C2 ATLL, SS Gain of function (F) 20,24  
PLCG1 D1165G Missense C2 ATLL Gain of function (F) 20  
CARD11 F902C Missense  ATLL Gain of function (F) 20  
CARD11 S547T Missense  New Gain of function (F)  
CARD11 F176C Missense Coiled coil New Gain of function (F)  
TRAF6 Q347X Stop gain Coiled coil /MATH New NA  
PI3K pathway PIK3R1 K141R Missense RHO-GAP New Probably gain of function (P)  
PIK3R1 Q475P Missense iSH2 New Probably gain of function (P)  
PIK3R1 T576A Missense iSH2 New Probably gain of function (P)  
PIK3R1 G680S Missense SH2 2 New Probably gain of function (P)  
PIK3R1 V704M Missense SH2 2 New Probably gain of function (P)  
PIK3R5 A259V Missense  Carcinoma (liver) Probably gain of function (P) 31  
PIK3CA L1001P Missense PI3K/PI4K New Probably gain of function (P)  
PDPK1 19_20del Inframe deletion  New NA  
PDPK1 151_152del Frameshift deletion Protein kinase New Probably loss of function (P)  
PDPK1 R324Q Missense Protein kinase New Probably gain of function (P)  
PDPK1 P340Q Missense Protein kinase New Probably gain of function (P)  
AKT1 G294R Missense Protein kinase New Probably gain of function (P)  
CTNNB1 T41A† Missense Phospho by GSK3b Hepatocellular carcinoma, acute lymphoblastic leukemia, breast cancer, Wilms’ tumor Gain of function (F) 32  
CTNNB1 H36P Missense  Hepatocellular carcinoma, acute lymphoblastic leukemia, breast cancer, Wilms’ tumor Gain of function (F) 32  
CTNNB1 S45F† Missense  Hepatocellular carcinoma, acute lymphoblastic leukemia, breast cancer, Wilms’ tumor Gain of function (F) 32  
CTNNB1 K335T Missense  Hepatocellular carcinoma Gain of function (F) 33  
AP-1/MAPK pathway KRAS I36M Missense  Hematopoeitic neoplasms Gain of function (F) 34  
KRAS A18D Missense GTP binding Lymphoma Gain of function (F) 34  
KRAS G13D Missense GTP binding Solid tumors Gain of function (F) 34  
MAPK3 R278Q Missense Protein kinase New Probably gain of function (P)  
STAT3 E616G Missense SH2 Lymphoma Gain of function (F) 26,35  
STAT3 E616K Missense SH2 Lymphoma Gain of function (F) 26,35  
GTF2I D317E Missense  New Probably gain of function (P)  
GTF2I N340S Missense  New Probably gain of function (P)  
GTF2I R523S Missense GTF2I-like New Probably gain of function (P)  
GTF2I L607F Missense GTF2I-like New Probably gain of function (P)  
GTF2I R702Q Missense  New Probably gain of function (P)  
GTPases pathway RHOA K18N Missense GTP binding New Gain of function (F)  
RHOA G17V Missense GTP binding AITL, ATLL Dominant negative (F) 12,-14,20,36  
VAV1 151_158del Frameshift deletion  New Probably loss of function (P)  
VAV1 778_783del Frameshift deletion  New Probably gain of function (P)  
VAV1 D797G Missense SH3 2 New Probably gain of function (P)  
VAV1 Y826S Missense SH3 2 New Probably gain of function (P)  
VAV2 Y214C Missense DH Gastric carcinoma Probably dominant negative (P)  
JAK/STAT and TLR pathways JAK1 D831E Missense Kinase New Probably gain of function (P)  
JAK2 V617F Missense  Myeloproliferative disorders Gain of function (F) 37,,,,,-43  
JAK3 A699V Missense Kinase Lymphoma, carcinoma Gain of function (F) 37,,,,,-43  
MYD88 S219C Missense TIR DLBCL, lymphocytic leukemia Probably gain of function (P) 44  

Genes are organized by functional groups.

AITL, angioimmunoblastic T-cell lymphoma; ATLL, adult T-cell lymphoma/leukemia; DLBCL, diffuse large B-cell lymphoma; F, functional validation; MF, mycosis fungoides; P, literature- and models-based; SS, Sézary syndrome.

*

Gene variants found in the same patient and in the same allele.

†

Gene variants found in the same patient but in different alleles.

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