Table 4.
Genetic alterations of diagnostic use and/or therapeutic or prognostic value in routine clinical practice in select NK- and T-cell neoplasms
| Disease subtype | Genes* | Frequency, % | Normal function | Technology used to detect | Prognostic marker† | Genotype-directed therapies | |
|---|---|---|---|---|---|---|---|
| ALCL | ALK rearrangement | 100% of ALK+ ALCL | Kinase | FISH | Favorable | ALK inhibitors | |
| DUSP22/IRF4 rearrangement | 30% of ALK− ALCL | Phosphatase | FISH | Favorable | |||
| TP63 rearrangement | 8% of ALK− ALCL | Tumor suppressor | FISH | Adverse | |||
| STAT3 | 38% of ALK− ALCL | JAK-STAT signaling intermediate | Sequencing | JAK/STAT inhibitors | |||
| AITL/PTCL | RHOA | 67/18 | GTPase | Sequencing | |||
| IDH2 | ∼13/0 | α-KG hydroxylase in TCA cycle | Sequencing | Trials of mutant IDH2 inhibitors | |||
| TET2 | ∼70/30 | DNA hydroxymethylation | Sequencing | Trials of hypomethylating agents | |||
| DNMT3A | ∼23/12 | DNA methyltransferase | Sequencing | ||||
| Other T/NK lymphoma | STAT3 | Up to 70% in LGL, 10% in γδ-TCL | JAK-STAT signaling intermediate | Sequencing | JAK/STAT inhibitors | ||
| STAT5B | Up to 35% in γδ-TCL | JAK-STAT signaling intermediate | Sequencing | Adverse in LGL | JAK/STAT inhibitors | ||
| SETD2 | Up to 90% in MEITL and 25% in γδ-TCL | H3K36 trimethyltransferase | Sequencing | ||||
| PLCγ | 15% in PTCL NOS | Component of TCR pathway | Sequencing | PLCγ inhibitors |
AITCL/PTCL, angioimmunoblastic T-cell lymphoma/peripheral T-cell lymphoma; ALCL, anaplastic large-cell lymphoma; TCL: T-cell lymphoma; LGL, large granular lymphocytic leukemia; MEITL, monomorphic epitheliotropic intestinal T-cell lymphoma; PLC, phospholipase C.
*
Mutations in gene names in bold are of diagnostic value.
†
Those genes left blank do not have clear prognostic relevance currently.