Key genetic alterations identified by NGS studies in lymphoid neoplasms
| Tumor type . | Genetic alteration . |
|---|---|
| T-ALL | PHF6, CNOT3, RPL5, RPL10 |
| ETP ALL | Loss-of-function mutations in hematopoietic regulators (GATA3, IKZF1, RUNX1, ETV6) |
| Gain-of-function mutations in Ras, FLT3, IL7R | |
| Inactivating mutations in epigenetic regulators (EZH2, SUZ12, EED, SETD2, DNMT3A) | |
| BCR-ABL1–like ALL | Rearrangement of CRLF2 in 50% of cases; concomitant activating JAK mutations in 50% of CRLF2-rearranged cases |
| Rearrangement of multiple kinase genes: ABL1, ABL2, EPOR, PDGFRB | |
| Hypodiploid ALL | Ras mutations (NF1, PTPN11, NRAS, KRAS) in near-haploid ALL |
| IKZF2 and TP53 mutations in low hypodiploid ALL; TP53 mutations are commonly germline, | |
| Relapsed ALL | CREBBP mutations enriched at relapse |
| NT5C2 mutations enriched at relapse | |
| Familial ALL | TP53 mutations in low-hypodiploid ALL; PAX5 p.Gly183Ser in autosomal-dominant ALL |
| DLBCL and NHL | Lymphoid signaling (CD79B) |
| NF-kB signaling (CARD11, MYD88) | |
| Histone modification (CREBBP/EP300, EZH2, MEF2B, MLL2/MLL3) | |
| SMZL | NOTCH2 mutations |
| MCL | NOTCH1 mutations, associated with poor outcome |
| HL | CIITA rearrangements |
| PMBCL | CIITA rearrangements |
| BL | TCF3/ID3 mutations in BL and other MYC-rearranged lymphomas |
| CCND mutations | |
| CLL | NOTCH1 mutations; associated with disease progression |
| mRNA splicing mutations (eg, SF3B1) | |
| DNA damage and/or repair mutations (ATM, POT1) | |
| Regulation of apoptosis (BIRC3) | |
| Innate immunity (MYD88, TLR2) | |
| HCL | Activating BRAF mutations |
| MM | Multiple targets of mutation, including NRAS, KRAS, TP53, CCND1, DIS3, BRAF, NF-κB signaling and histone modification |
| WM | MYD88 p.Leu265Pro in >90% of cases |
| Tumor type . | Genetic alteration . |
|---|---|
| T-ALL | PHF6, CNOT3, RPL5, RPL10 |
| ETP ALL | Loss-of-function mutations in hematopoietic regulators (GATA3, IKZF1, RUNX1, ETV6) |
| Gain-of-function mutations in Ras, FLT3, IL7R | |
| Inactivating mutations in epigenetic regulators (EZH2, SUZ12, EED, SETD2, DNMT3A) | |
| BCR-ABL1–like ALL | Rearrangement of CRLF2 in 50% of cases; concomitant activating JAK mutations in 50% of CRLF2-rearranged cases |
| Rearrangement of multiple kinase genes: ABL1, ABL2, EPOR, PDGFRB | |
| Hypodiploid ALL | Ras mutations (NF1, PTPN11, NRAS, KRAS) in near-haploid ALL |
| IKZF2 and TP53 mutations in low hypodiploid ALL; TP53 mutations are commonly germline, | |
| Relapsed ALL | CREBBP mutations enriched at relapse |
| NT5C2 mutations enriched at relapse | |
| Familial ALL | TP53 mutations in low-hypodiploid ALL; PAX5 p.Gly183Ser in autosomal-dominant ALL |
| DLBCL and NHL | Lymphoid signaling (CD79B) |
| NF-kB signaling (CARD11, MYD88) | |
| Histone modification (CREBBP/EP300, EZH2, MEF2B, MLL2/MLL3) | |
| SMZL | NOTCH2 mutations |
| MCL | NOTCH1 mutations, associated with poor outcome |
| HL | CIITA rearrangements |
| PMBCL | CIITA rearrangements |
| BL | TCF3/ID3 mutations in BL and other MYC-rearranged lymphomas |
| CCND mutations | |
| CLL | NOTCH1 mutations; associated with disease progression |
| mRNA splicing mutations (eg, SF3B1) | |
| DNA damage and/or repair mutations (ATM, POT1) | |
| Regulation of apoptosis (BIRC3) | |
| Innate immunity (MYD88, TLR2) | |
| HCL | Activating BRAF mutations |
| MM | Multiple targets of mutation, including NRAS, KRAS, TP53, CCND1, DIS3, BRAF, NF-κB signaling and histone modification |
| WM | MYD88 p.Leu265Pro in >90% of cases |
PMBCL, primary mediastinal B-cell lymphoma.