Table 3.
Genetic alterations of diagnostic use and/or therapeutic or prognostic value in routine clinical practice in select B-cell lymphoid neoplasms
| Disease subtype | Genes* | Frequency, % | Normal function | Technology used to detect | Prognostic marker† | Genotype-directed therapies |
|---|---|---|---|---|---|---|
| CLL/SLL | NOTCH1 | Up to 15 | Notch pathway | Sequencing | Adverse | Trials of NOTCH inhibitors |
| SF3B1 | 15-20 | mRNA splicing | Sequencing | Adverse | ||
| TP53 mutation or deletion | 7-15 | Tumor suppressor | Sequencing and cytogenetic/ FISH analysis | Adverse | ||
| ATM mutation or deletion | 9-12 | Tumor suppressor | Adverse | |||
| LPL | MYD88 | ∼90 | Couples TLR to NF-κB | Sequencing | BTK inhibitors | |
| CXCR4 | ∼30 | Chemokine receptor | Sequencing | Trials of CXCR4 inhibitors | ||
| HCL | BRAF | ∼100 | MAPK pathway | Sequencing | BRAF inhibitors | |
| MAP2K1‡ | ∼50% in HCL-v | MAPK pathway | Sequencing | Adverse | ||
| FL/GCB DLBCL | BCL2 | 50-90 | Antiapoptotic | FISH | Venetoclax | |
| KMT2D/MLL2 | 89/27 | H3K4 methyltransferase | Sequencing | |||
| CREBBP | 41/42 | Histone acetyltransferase | Sequencing | Trials of HDAC inhibitors | ||
| EP300 | 9/10 | Histone acetyltransferase | Sequencing | |||
| EZH2 | 7/22 | H3K27 methyltransferase | Sequencing | Trials of EZH2 inhibitors | ||
| MEF2B | 13/8-18 | Transcription factor | Sequencing | |||
| MAP2K1‡ | 43% in pediatric-type FL | MAPK pathway | Sequencing | |||
| ABC DLBCL | MYD88 | 29 | Couples TLR to NF-κB | Sequencing | Trials of IRAK1/4 inhibitors | |
| CARD11 | 10 | Couples BCR to NF-κB | Sequencing | Trials of MALT1 inhibitors | ||
| CD79A/CD79B | 3/18 | Components of BCR | Sequencing | Trials of BTK, SYK inhibitors | ||
| TNFAIP3 | 57 | Inhibits NF-κB | Sequencing | Proteasome inhibitors | ||
| Burkitt | MYC | ∼100 | Transcription factor | FISH | Trials of BET inhibitors | |
| ID3 | ∼70 | Inhibitors of TCF3 | Sequencing | |||
| TCF3 | ∼30 | Regulates mTOR pathway | Sequencing | |||
| MCL | t(11;14)(q13;q32); IG/CCND1 translocations | 80%-90% | Cell cycle regulator | FISH | ||
| IG/CCND2 translocations | ∼50% of CCND1− MCL | FISH | ||||
| NOTCH1/2 | 10-15 | Signaling molecule involved in cell differentiation | Sequencing | Adverse | ||
| cHL/PMBL | PD-L1/L2 | ∼95 | Inhibit T-cell activation | PD-1/PD-L1 blockade | ||
| B2M | 70/64 | MHC class I coexpression | Sequencing | Favorable | ||
| TNFAIP3 | 44-60/36 | Inhibits NF-κB | Sequencing | |||
| PTPN1 | 20/22 | Phosphatase | Sequencing | |||
| PCM/MM | Hyperdiploidy | 50 | Chr. 3, 5, 7, 9, 11, 15, 19 and/or 21 | FISH or SNP array | Favorable | |
| t(11;14) | 15-20 | Cyclin D1 | FISH | Unfavorable if CCND1 mutated, otherwise neutral | ||
| t(4;14) | 15 | FGFR3/MMSET | FISH | Unfavorable | ||
| t(14;16)/ t(14;20) | 5/1 | c-MAF/MAFB (upregulate cyclin D2) | FISH | Unfavorable | ||
| t(6;14) | 1 | Cyclin D3 | FISH | Unfavorable | ||
| 1q gain/del(1p)/del(17p) | 40/30/10 | FISH or SNP array | Unfavorable | |||
| MYC translocations | 15-20 | MYC upregulation | FISH | Unfavorable | ||
| KRAS/NRAS/BRAF | 20/20/10 | Components of MAPK pathway | Sequencing |
ABC DLBCL, activated B-cell diffuse large B-cell lymphoma; BCR, B-cell receptor; BET, bromodomain and extraterminal; BTK, Bruton tyrosine kinase; cHL/PMBL, classical Hodgkin lymphoma/primary mediastinal B-cell lymphoma; Chr., chromosome; CLL/SLL, chronic lymphocytic leukemia/small lymphocytic lymphoma; FL/GCB DLBCL, follicular lymphoma/germinal center B-cell lymphoma; HCL, hairy cell leukemia; HCL-v, HCL-variant; HDAC, histone deacetylase; LPL, lymphoplasmacytic lymphoma; MCL, mantle cell lymphoma; MHC, major histocompatibility complex; mTOR, mammalian target of rapamycin; PCM/MM, plasma cell myeloma/multiple myeloma; SNP, single-nucleotide polymorphism; TLR, Toll-like receptor.
Mutations in gene names in bold are of diagnostic value.
Those genes left blank do not have clear prognostic relevance currently.
MAP2K1 mutations are detected in HCL-v and HCL expressing IGHV4-34, and pediatric-type FL.