Oncogenic genes deregulated by chromosomal translocations in B-cell non-Hodgkin's lymphoma.
| Histology . | Chromosomal Translocation . | Activated Gene or Fusion Gene . | Mechanism of Activation . | Predominant Structural/Functional Features of Altered Gene(s) . | Frequency . |
|---|---|---|---|---|---|
| Follicular center cella | t(14; 18)(q32;q21) | BCL2 | Relocation to IgH locus | Anti-apoptosis protein | 80% |
| Follicular center cell | t(1;22)(q22;q11) | FCGR2B | Relocation to IgL locus | ITIM-containing low affinity Ig Fc receptor | < 1% |
| Small noncleaved cellb | t(8;14)(q24;q32) | cMYC | Relocation to IgH locus | bHLH/zip transcription factor | |
| t(2;8)(p12;q24) | cMYC | Relocation to IgK locus | bHLH/zip transcription factor | 100% | |
| t(8;22)(q24;q11) | cMYC | Relocation to IgL locus | bHLH/zip transcription factor | ||
| DLCLc | t(3;14)(q27;q32) | BCL6 | Relocation to IgH locus | Zinc finger transcription factor | |
| t(3;22)(q27;q11) | BCL6 | Relocation to IgL locus | Zinc finger transcription factor | ||
| t(2;3)(p12;q27) | BCL6 | Relocation to IgK locus | Zinc finger transcription factor | 30-40% | |
| t(3;4)(q27;p11) | BCL6 | Relocation to TTF locusd | Zinc finger transcription factor | ||
| t(3;11)(q27;q23) | BCL6 | Relocation to BOB1/OBF1 locusd | Zinc finger transcription factor | ||
| DLCL | t(14;15)(q32;q11-13) | BCL8 | Relocation to IgH locus | No homology with known proteins | <5% |
| Mantle cell | t(11;14)(q13;q32) | CCND1 (cyclin D1) | Relocation to IgH locus | G1 cyclin | >95% |
| Lymphoplasmacytoid | t(9;14)(p13;q32) | PAX5 | Relocation to IgH locus | Paired homeobox transcription factor | 50% |
| MALT | t(11;18)(q21;q21) | AP12-MLT/MALT1 | Gene fusion | Anti-apoptosis protein (API2), unknown (MLT/MALT1) | 19-36% |
| MALT | t(1;14)(p22;q32) | BCL10 | Relocation to IgH locus | Apoptosis regulatory protein | <5% |
| Splenic MZ lymphoma | t(2;7)(p12;q21) | CDK6 | Relocation to IgK locus | Cell cycle kinase | <5% |
| t(7;14)(q21;q32) | CDK6 | Relocation to IgH locus | Cell cycle kinase | ||
| B-NHL | t(10;14)(q24;q32) | LYT10(NFKB2) | Relocation to IgH locus | REL transcription factor homology | <1% |
| CLL/B-NHL | t(14;19)(q32;q13.1) | BCL3 | Relocation to IgH locus | IκB | <1% |
| B-NHL | ins(2;2)(p13;p11.2-14) | REL-NRG | Gene fusion | Transcription factor (REL), unknown (NRG) | <1% |
| pre-B ALL (B-NHL ?) | t(5;14)(q31;q32) | IL3 | Relocation to IgH locus | Growth factor | <1% |
| pre-B ALL/B-NHL | t(1;14)(q21;q32) | BCL9 | Relocation to IgH locus | No homology with known proteins | <1% |
| B-NHL | t(1;14)(q21;q32) | MUC1 | Relocation to IgH locus | Mucin-like glycoprotein | ∼5% |
| Myeloma/B-NHL | t(1;14)(q21;q32) | MUM-2 | Relocation to IgH locus | Fc receptor-related proteins | * |
| MUM-3 | |||||
| B-NHL | t(11;14)(q23;q32) | DDX6/RCK | Relocation to IgH locus | DEAD box protein/RNA helicase | <1% |
| B-NHL | t(12;22)(q13;q11) | CCND2(cyclin D2) | Relocation to IgL locus | G1 cyclin | <1% |
| B-NHL | t(12;14)(q24;q32) | BCL7A | Relocation to IgH locus | Unknown function, weak homology to the actin-binding protein caldesmon | <1% |
| The histologic spectrum of B-NHLs affected by most of the less frequent translocations has not been determined. | |||||
| Histology . | Chromosomal Translocation . | Activated Gene or Fusion Gene . | Mechanism of Activation . | Predominant Structural/Functional Features of Altered Gene(s) . | Frequency . |
|---|---|---|---|---|---|
| Follicular center cella | t(14; 18)(q32;q21) | BCL2 | Relocation to IgH locus | Anti-apoptosis protein | 80% |
| Follicular center cell | t(1;22)(q22;q11) | FCGR2B | Relocation to IgL locus | ITIM-containing low affinity Ig Fc receptor | < 1% |
| Small noncleaved cellb | t(8;14)(q24;q32) | cMYC | Relocation to IgH locus | bHLH/zip transcription factor | |
| t(2;8)(p12;q24) | cMYC | Relocation to IgK locus | bHLH/zip transcription factor | 100% | |
| t(8;22)(q24;q11) | cMYC | Relocation to IgL locus | bHLH/zip transcription factor | ||
| DLCLc | t(3;14)(q27;q32) | BCL6 | Relocation to IgH locus | Zinc finger transcription factor | |
| t(3;22)(q27;q11) | BCL6 | Relocation to IgL locus | Zinc finger transcription factor | ||
| t(2;3)(p12;q27) | BCL6 | Relocation to IgK locus | Zinc finger transcription factor | 30-40% | |
| t(3;4)(q27;p11) | BCL6 | Relocation to TTF locusd | Zinc finger transcription factor | ||
| t(3;11)(q27;q23) | BCL6 | Relocation to BOB1/OBF1 locusd | Zinc finger transcription factor | ||
| DLCL | t(14;15)(q32;q11-13) | BCL8 | Relocation to IgH locus | No homology with known proteins | <5% |
| Mantle cell | t(11;14)(q13;q32) | CCND1 (cyclin D1) | Relocation to IgH locus | G1 cyclin | >95% |
| Lymphoplasmacytoid | t(9;14)(p13;q32) | PAX5 | Relocation to IgH locus | Paired homeobox transcription factor | 50% |
| MALT | t(11;18)(q21;q21) | AP12-MLT/MALT1 | Gene fusion | Anti-apoptosis protein (API2), unknown (MLT/MALT1) | 19-36% |
| MALT | t(1;14)(p22;q32) | BCL10 | Relocation to IgH locus | Apoptosis regulatory protein | <5% |
| Splenic MZ lymphoma | t(2;7)(p12;q21) | CDK6 | Relocation to IgK locus | Cell cycle kinase | <5% |
| t(7;14)(q21;q32) | CDK6 | Relocation to IgH locus | Cell cycle kinase | ||
| B-NHL | t(10;14)(q24;q32) | LYT10(NFKB2) | Relocation to IgH locus | REL transcription factor homology | <1% |
| CLL/B-NHL | t(14;19)(q32;q13.1) | BCL3 | Relocation to IgH locus | IκB | <1% |
| B-NHL | ins(2;2)(p13;p11.2-14) | REL-NRG | Gene fusion | Transcription factor (REL), unknown (NRG) | <1% |
| pre-B ALL (B-NHL ?) | t(5;14)(q31;q32) | IL3 | Relocation to IgH locus | Growth factor | <1% |
| pre-B ALL/B-NHL | t(1;14)(q21;q32) | BCL9 | Relocation to IgH locus | No homology with known proteins | <1% |
| B-NHL | t(1;14)(q21;q32) | MUC1 | Relocation to IgH locus | Mucin-like glycoprotein | ∼5% |
| Myeloma/B-NHL | t(1;14)(q21;q32) | MUM-2 | Relocation to IgH locus | Fc receptor-related proteins | * |
| MUM-3 | |||||
| B-NHL | t(11;14)(q23;q32) | DDX6/RCK | Relocation to IgH locus | DEAD box protein/RNA helicase | <1% |
| B-NHL | t(12;22)(q13;q11) | CCND2(cyclin D2) | Relocation to IgL locus | G1 cyclin | <1% |
| B-NHL | t(12;14)(q24;q32) | BCL7A | Relocation to IgH locus | Unknown function, weak homology to the actin-binding protein caldesmon | <1% |
| The histologic spectrum of B-NHLs affected by most of the less frequent translocations has not been determined. | |||||
BCL2 deregulation also occurs in 10-30% of DLCL and ∼30% of marginal zone lymphomas.
cMYC deregulation is also seen in ∼10% of DLCL.
Approximately 6-15% of follicular center cell and 10% of marginal zone lymphomas also have BCL6 deregulation.
Many other non-Ig loci have been reported also to deregulate BCL6.
Not yet determined