Common primary and secondary cytogenetic abnormalities in multiple myeloma
| . | Abnormality/locus . | Genes involved . | Frequency, % . | Characteristics . | Prognosis/risk . |
|---|---|---|---|---|---|
| Primary abnormalities | Hyperdiploidy | Many/unknown | 50 | Highly associated with lytic bone disease, often as the only disease manifestation Associated with “exceptional response” to lenalidomide | Standard/low |
| t(6;14)(p21;q32) | CCND3 | <5 | Similar to hyperdiploidy | Standard/low | |
| t(11;14)(q13;q32) | CCND1 | 15-20 | Lymphoplasmacytoid appearance, often with B-cell expression profile High rates of free light chain only, oligosecretory, nonsecretory, and IgM/IgD myeloma Most common abnormality in primary PCL and AL amyloidosis | Intermediate | |
| t(4;14)(p16;q32) | MMSET (WHSC1) | 10-15 | Large, atypical appearance of plasma cells Frequently co-occurs with +1q May derive particular benefit from proteasome inhibitors compared to chemo | High | |
| t(14;16)(q32;q23) | MAF | 5 | Frequently associated with high circulating free light chains and renal failure Frequent association with APOBEC mutations Second most common abnormality in PCL | High | |
| t(14;20)(q32;q12) | MAFb | <5 | Similar to t(14;16) | High | |
| Secondary abnormalities | +1q Gain(1q) [3 copies] Amp(1q) [4 copies] | Many (CKS1B, MCL1, IL-6R, PBX-1, ADAR1, SLAMF7, FcHR5) | 40 30 10 | Can co-occur with standard-risk or high-risk cytogenetics; more strongly associated with high risk “Jumping 1q” syndrome associated with genomic instability Copy number can increase over time | High Risk increases as copy number rises |
| Del(1p) | CDKN2C, FAM46C | 5-10 | High | ||
| Del(17p) | TP53 | 5-20 | Can be acquired at any time in disease process Higher proliferative rate and LDH Prognosis may be dependent on clonal fraction and/or coexistent TP53 mutation | High | |
| MYC rearrangement | MYC | 40 (all SV types) 5-10 (immunoglobulin translocation) | Associated with higher disease burden and β2M Commonly seen in hyperdiploid subset, rarely with t(11;14) | High Prognosis depends on type of rearrangement, worse for IgH/IgL translocations | |
| −13 | RB1, DIS3, others | ~50 | Very commonly identified in both standard and high-risk patients, more frequent in high risk | No impact; possibly high risk if found on karyotype | |
| Hypodiploidy | Many | ~20 | Defined as loss of chromosomal material On karyotype, 45 or fewer chromosomes; on FISH, can manifest with loss of IgH, MAF, or other probes | High |
| . | Abnormality/locus . | Genes involved . | Frequency, % . | Characteristics . | Prognosis/risk . |
|---|---|---|---|---|---|
| Primary abnormalities | Hyperdiploidy | Many/unknown | 50 | Highly associated with lytic bone disease, often as the only disease manifestation Associated with “exceptional response” to lenalidomide | Standard/low |
| t(6;14)(p21;q32) | CCND3 | <5 | Similar to hyperdiploidy | Standard/low | |
| t(11;14)(q13;q32) | CCND1 | 15-20 | Lymphoplasmacytoid appearance, often with B-cell expression profile High rates of free light chain only, oligosecretory, nonsecretory, and IgM/IgD myeloma Most common abnormality in primary PCL and AL amyloidosis | Intermediate | |
| t(4;14)(p16;q32) | MMSET (WHSC1) | 10-15 | Large, atypical appearance of plasma cells Frequently co-occurs with +1q May derive particular benefit from proteasome inhibitors compared to chemo | High | |
| t(14;16)(q32;q23) | MAF | 5 | Frequently associated with high circulating free light chains and renal failure Frequent association with APOBEC mutations Second most common abnormality in PCL | High | |
| t(14;20)(q32;q12) | MAFb | <5 | Similar to t(14;16) | High | |
| Secondary abnormalities | +1q Gain(1q) [3 copies] Amp(1q) [4 copies] | Many (CKS1B, MCL1, IL-6R, PBX-1, ADAR1, SLAMF7, FcHR5) | 40 30 10 | Can co-occur with standard-risk or high-risk cytogenetics; more strongly associated with high risk “Jumping 1q” syndrome associated with genomic instability Copy number can increase over time | High Risk increases as copy number rises |
| Del(1p) | CDKN2C, FAM46C | 5-10 | High | ||
| Del(17p) | TP53 | 5-20 | Can be acquired at any time in disease process Higher proliferative rate and LDH Prognosis may be dependent on clonal fraction and/or coexistent TP53 mutation | High | |
| MYC rearrangement | MYC | 40 (all SV types) 5-10 (immunoglobulin translocation) | Associated with higher disease burden and β2M Commonly seen in hyperdiploid subset, rarely with t(11;14) | High Prognosis depends on type of rearrangement, worse for IgH/IgL translocations | |
| −13 | RB1, DIS3, others | ~50 | Very commonly identified in both standard and high-risk patients, more frequent in high risk | No impact; possibly high risk if found on karyotype | |
| Hypodiploidy | Many | ~20 | Defined as loss of chromosomal material On karyotype, 45 or fewer chromosomes; on FISH, can manifest with loss of IgH, MAF, or other probes | High |
AL, amyloid light chain; SV, structural variant.