Plasma Cell Neoplasms Tables: Recurrent Cytogenomic Alterations
Table 1 - Clinically significant cytogenomic alterations in plasma cell myeloma (Literature Review). Summary table reviewing 65 papers applying FISH, CMA, NGS, and gene expression profiling for PCN diagnosis and prognosis. See Table 2 for references and Level 3 evidence. Table derived from Pugh et al., 2018 [PMID 30393007] with permission from Cancer Genetics.
| Evidence Level | Chromosomal Abnormality | Significance | Genes |
| Level 1
well established evidence in NCCN guideline, WHO criteria, FDA-approved, COG recommendation, or based on large body of publications. |
Hyperdiploidy (+3, +5, +7, +9, +11, +15, +21) | Good prognosis | |
| t(4;14) | Poor prognosis, predicts bortezomib response | IGH | |
| t(6;14) | Good prognosis | IGH | |
| t(14;16) | Poor prognosis | IGH | |
| t(11;14) | Good prognosis | IGH | |
| t(14;20) | Poor prognosis | ||
| del(1p) | Poor prognosis | ||
| 1q+ | Poor prognosis | ||
| del(13q) | Poor prognosis | ||
| 16q | Poor prognosis | ||
| del(17p) | Poor prognosis (Level 1), predicts response (Level 2) | ||
| Level 2
emerging evidence by one large study or multiple case reports |
1p CN-LOH | Recurrent | |
| +2 | Recurrent | ||
| del(4q) | Recurrent | ||
| del(5p), 5q+, del(5q) | Recurrent | ||
| 6p+ | Recurrent | ||
| del(6q) | Recurrent | ||
| 7q+ | Recurrent | ||
| del(8p) | Recurrent | ||
| 8q24.2+ | Recurrent | MYC | |
| 9p+ | Recurrent | ||
| del(10q23.31) | Recurrent | PTEN | |
| 11q+ | Recurrent | ||
| del(12p) or 12p CN-LOH | Recurrent | ||
| del(13q32.2) | Recurrent | TGDS | |
| del(14q) | Good prognosis | ||
| 14q CN-LOH | Recurrent | ||
| 16 CN-LOH | Recurrent | ||
| 17 CN-LOH | Recurrent | ||
| 17q25+ | Recurrent | ||
| +18 | Recurrent | ||
| +19, 19q+ | Recurrent | ||
| del(20p) | Recurrent | ||
| +20, 20q+ | Recurrent | ||
| del(22) | Recurrent | ||
| 22q21+ | Associated with relapse | PRAME | |
| del(X), X+, X CN-LOH | Recurrent | ||
| Xq+ in males | Poor prognosis |
Table 2 - Recurrent Abnormalities of copy number aberration (CNAs) and copy-neutral loss-of-heterozygosity (cnLOH) in plasma cell myeloma (Literature Review). Table derived from Pugh et al., 2018 [PMID 30393007] with permission from Cancer Genetics.
| Chromosome | Region (whole chromosome or segmental, including cytobands) | Abnormality Type (gain, loss, LOH) | Relevant genes (if known) | Significance (Recurrent, Diagnostic, Prognostic, Targeted treatment) | Strength of Evidence (Level 1, 2, 3, see legend below table for criteria) | References |
| 1 | 1p32 | Loss | FAF1, CDKN2C | Poor prognostic marker | 1, 2 | [1] [2] [3] |
| 1p22.2-p22.1 | Loss | BARHL2, TGFBR3, and others; HSP90B3P, TGFER3, BRDT, EPHAX4, BTBD8 | Prognostic | 1, 3 | [2] [3] [4] | |
| 1p21.3 | Loss | SNX7 | Recurrent | 2 | [5] | |
| 1p13.2 | Loss | MAGI3, BCL2 like and others | Recurrent | 3 | [6] | |
| 1p12 | Loss | MAN1A2, FAM46C, GDAP2 | Recurrent | 2 | [1] [2] | |
| 1p | cnLOH | Recurrent | 2 | [3] | ||
| 1p | Loss | Recurrent | 1 | [2] [6] [7] [8] [9] | ||
| 1q21.2-q23 | Gain | CKS1B and ANP32E | Recurrent | 1 | [2] [6] [7] [8] [9] | |
| 1q | Gain | Poor prognostic marker | 1 | [2] [6] [7] [8] | ||
| 2 | 2 | Gain | Recurrent | 2 | [8] | |
| 2q | Loss | Recurrent | 3 | [7] | ||
| 3 | 3 | Gain | Recurrent | 1 | [2] [6] [7] [8] | |
| 3q21-23 | Gain | Recurrent | 2 | [3] | ||
| 4 | 4p16.3 | Loss | FGFR3 and WHSC1 | Recurrent | 3 | [2] |
| 4p15.2 | Loss | LGI2, SEPSECS, PI4K2B and others | Recurrent | 3 | [2] | |
| 4q35.1 | Loss | DCTD, ING2 and others | Recurrent | 2 | [4] | |
| 5 | 5 | Gain | Recurrent | 1 | [2] [6] [7] [8] [9] | |
| 5p | Gain | Recurrent | 3 | [2] | ||
| 5p | Loss | Recurrent | 2 | [8] | ||
| 5p14.3 | Gain | CDH10, CDH12 | Recurrent | 3 | [6] | |
| 5q | Gain | Recurrent | 2 | [2] [3] | ||
| 5q13.2 | Loss | OCLN, NAIP and others | Recurrent | 2 | [4] | |
| 6 | 6p | Gain | Recurrent | 2 | [1] [2] [8] | |
| 6pter-p22.3 | Gain | Recurrent | 3 | [2] | ||
| 6q | Loss | Poor prognostic marker | 2 | [1] [2] [3] [6] [7] [8] | ||
| 6q11.1-q13 | Gain | MTRNR2L9 | Recurrent | 3 | [4] | |
| 6q16.3 | Loss | COQR, GRIK2 | Recurrent | 3 | [2] | |
| 6q25.3 | Loss | IGFR3 | Recurrent | 3 | [6] | |
| 7 | 7 | Gain | Recurrent | 1 | [2] [6] [7] [8] | |
| 7p | Gain | Recurrent | 3 | [2] | ||
| 7p15.2 | Gain | CBX3, etc | Recurrent | 3 | [4] | |
| 7q | Gain | Recurrent | 2 | [2] [3] | ||
| 8 | 8p | Loss | Recurrent | 2 | [1] [2] [3] [6] [7] [8] | |
| 8p23.1 | Loss | DEFB4 and others | Recurrent | 2 | [4] | |
| 8p21.3/p21.2 | Loss | TNFRSF10B, DOCK5 and others | Recurrent | 3 | [6] | |
| 8q | Gain | Recurrent | 3 | [2] | ||
| 8q24.2 | Gain/amplification and Loss | MYC | Recurrent | 2 | [2] [6] [9] [10] [11] | |
| 8q24.3 | Gain | MAPK15, TOP1MT, CYP11B11 (P450), ZNF41, ZNF517, ZNF616 and ZNF707 | Recurrent | 3 | [6] [11] | |
| 9 | 9 | Gain | Recurrent | 1 | [2] [6] [7] [8] | |
| 9p | Gain | Recurrent | 2 | [2] [3] | ||
| 9q | Gain | Recurrent | [2] [3] | |||
| 9q34.3 | Gain | ZNF79, CDK9, SET | Recurrent | 3 | [6] | |
| 10 | 10p | Loss | Recurrent | 3 | [2] | |
| 10q | Loss | Recurrent | 3 | [2] | ||
| 10q23.31 | Loss | PTEN | Recurrent | 2 | [12] | |
| 11 | 11 | Gain | Recurrent | 1 | [2] [6] [7] [8] | |
| 11p | Gain | Recurrent | 3 | [2] | ||
| 11q | Gain | Recurrent | 2 | [3] [7] | ||
| 11q13.1/q13.4 | Gain | SCYL1, MAP3K11, CCND1, FGF4, FGF3, NUMA and RELT | Recurrent | 3 | [6] | |
| 11q22 | Loss | Recurrent | 3 | [2] | ||
| 11q22.1-q22.3 | Homozygous Loss | BIRC3, BIRC2, MMP cluster | Recurrent | 3 | [2] [13] | |
| 12 | 12p | Loss | Recurrent | 2 | [1] [2] [6] [8] | |
| 12p | LOH | Recurrent | 2 | [3] [8] | ||
| 12p13.1 | Loss | CDKN1B, APOLD1 | Recurrent | 3 | [2] | |
| 13 | 13q/13 | Loss | Poor prognostic marker | 1 | [2] [3] [8] [7] [6] [9] | |
| 13q14.11/q14.2 | Loss | TNFSF11, RB1, P2RY5, RCBTB2 | Poor prognostic marker | 1 | [1] [2] [6] | |
| 13q32.2 | Loss | TGDS | Recurrent | 2 | [5] | |
| 14 | 14q/14 | Loss | Better prognostic marker | 2 | [1] [2] [3] [6] [7] [8] | |
| 14q/14 | Gain | Recurrent | 3 | [7] | ||
| 14q | cnLOH | Recurrent | 2 | [3] [8] | ||
| 14q24.1-q24.3 | Loss | MLH3 | Recurrent | 2 | [4] | |
| 14q32.32 | Homozygous Loss | RCOR1, TRAF3, AMN, CDC42BPB | Recurrent | 3 | [2] | |
| 15 | 15 | Gain | Recurrent | 1 | [2] [3] [6] [7] [8] | |
| 15q24.1 | Gain | CYP11A1, ARID3B, CSK, etc. | Recurrent | 3 | [4] | |
| 16 | 16p11.2 | Loss | TP53TG3 | Recurrent | 3 | [4] |
| 16q | Loss | Recurrent | 1 | [1] [2] [6] [7] [8] | ||
| 16q12.1-q12.2 | Homozygous Loss | CYLD, SALL1 | Recurrent | 3 | [2] | |
| 16q24.3 | Loss | CBFA2T3 and others | Recurrent | 3 | [6] | |
| 16 | cnLOH | Recurrent | 2 | [8] | ||
| 17 | 17p/17 | Gain | Recurrent | 3, 3 | [2] [7] | |
| 17p | Loss | Predictive & prognostic | 1 | [5] [6] [7] [8] | ||
| 17p13 | Loss | ATP1B2, TP53, WRAP5, EFNB3 | Predictive & prognostic | 1 | [2] [9] | |
| 17 | cnLOH | Recurrent | 2 | [8] | ||
| 17q21.33 and 17qter | Gain | Recurrent | 3 | [2] | ||
| 17q25 | Gain | Recurrent | 2 | [8] | ||
| 18 | 18 | Gain | Recurrent | 2, 3 | [2] [8] | |
| 19 | 19 | Gain | Recurrent | 2 | [2] [6] [7] [8] | |
| 19p/ 19p13 | Gain | ICAM4, ICAM4, IBCL2L12, TYK2, IL2 and DNMT1 | Recurrent | 3 | [2] [4] [6] | |
| 19q | Gain | Recurrent | 2 | [2] [3] | ||
| 20 | 20p | Loss | Recurrent | 2 | [2] [8] | |
| 20/20q | Gain | Recurrent | 2 | [2] [8] | ||
| 20/20q | Loss | Recurrent | 3 | [2] [7] | ||
| 21 | 21 | Gain | Recurrent | 1 | [2] [6] [7] [8] | |
| 22 | 22 | Loss | Recurrent | 2 | [1] [2] [6] [7] [8] | |
| 22q21 | mostly Gain | PRAME | Recurrent, Associated with relapse | 2 | [11] | |
| X | X | Gain / Loss | Recurrent | 2 | [3] [8] | |
| X | LOH | Recurrent | 2 | [3] | ||
| Xp | Loss | Recurrent | 3 | [2] | ||
| Xp22.33 | Loss | SHOX, CRLF2, IL3RA | Recurrent | 3 | [4] | |
| Xq | Gain (in males) | Poor prognostic marker | 2 | [1] [2] | ||
| Xq | Loss | Recurrent | 3 | [2] | ||
| Xq21.31-q21.32 | Loss | PABPC5, PCDHX | Recurrent | 3 | [4] | |
| Xq27.3-q28 | Gain | AFF2, MTMR1, etc | Recurrent | 3 | [4] | |
| Y | Y | Loss | 2 | [1] | ||
| Genome wide load of CNA > 100Mb | Gain / Loss | associated with significant change in GEP at relapse | 2 | [11] |
cnLOH = copy neutral LOH, LOH = Loss of Heterozygosity, GEP = Gene Expression Profile
Level of evidence:
Level 1: well established evidence (in NCCN guideline, WHO criteria, FDA-approved, COG recommendation, or based on large body of publications)
Level 2: emerging evidence (by one large study or multiple case reports)
Level 3: presumptive evidence (multiple case reports or expert opinion)
Reference
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 B, Hebraud; et al. (2015). "Role of additional chromosomal changes in the prognostic value of t(4;14) and del(17p) in multiple myeloma: the IFM experience". doi:10.1182/blood-2014-07-587964. PMC 4375107. PMID 25636340.CS1 maint: PMC format (link)
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 2.31 2.32 2.33 2.34 2.35 2.36 2.37 2.38 2.39 2.40 2.41 2.42 2.43 2.44 2.45 2.46 2.47 2.48 2.49 2.50 2.51 2.52 2.53 2.54 J, Smetana; et al. (2014). "Genome-wide screening of cytogenetic abnormalities in multiple myeloma patients using array-CGH technique: a Czech multicenter experience". doi:10.1155/2014/209670. PMC 4060785. PMID 24987674.CS1 maint: PMC format (link)
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 M, Kim; et al. (2015). "Copy number variations could predict the outcome of bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma". PMID 25145975.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 E, Kjeldsen (2016). "Identification of Prognostically Relevant Chromosomal Abnormalities in Routine Diagnostics of Multiple Myeloma Using Genomic Profiling". PMID 26912802.
- ↑ 5.0 5.1 5.2 N, Bolli; et al. (2014). "Heterogeneity of genomic evolution and mutational profiles in multiple myeloma". doi:10.1038/ncomms3997. PMC 3905727. PMID 24429703.CS1 maint: PMC format (link)
- ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.22 6.23 6.24 6.25 6.26 6.27 6.28 6.29 T, Boneva; et al. (2014). "Can genome array screening replace FISH as a front-line test in multiple myeloma?". PMID 24757046.
- ↑ 7.00 7.01 7.02 7.03 7.04 7.05 7.06 7.07 7.08 7.09 7.10 7.11 7.12 7.13 7.14 7.15 7.16 7.17 7.18 7.19 7.20 7.21 7.22 Bk, Zehentner; et al. (2012). "Array-based karyotyping in plasma cell neoplasia after plasma cell enrichment increases detection of genomic aberrations". PMID 23010713.
- ↑ 8.00 8.01 8.02 8.03 8.04 8.05 8.06 8.07 8.08 8.09 8.10 8.11 8.12 8.13 8.14 8.15 8.16 8.17 8.18 8.19 8.20 8.21 8.22 8.23 8.24 8.25 8.26 8.27 8.28 8.29 8.30 M, Stevens-Kroef; et al. (2012). "High detection rate of clinically relevant genomic abnormalities in plasma cells enriched from patients with multiple myeloma". PMID 22833442.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 N, Bolli; et al. (2016). "A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma". doi:10.1038/bcj.2016.72. PMC 5056967. PMID 27588520.CS1 maint: PMC format (link)
- ↑ K, Rack; et al. (2016). "Genomic profiling of myeloma: the best approach, a comparison of cytogenetics, FISH and array-CGH of 112 myeloma cases". PMID 26338801.
- ↑ 11.0 11.1 11.2 11.3 P, Krzeminski; et al. (2016). "Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse". doi:10.18632/oncotarget.13025. PMC 5348347. PMID 27811368.CS1 maint: PMC format (link)
- ↑ H, Chang; et al. (2006). "Analysis of PTEN deletions and mutations in multiple myeloma". PMID 16112193.
- ↑ Jb, Egan; et al. (2012). "Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides". doi:10.1182/blood-2012-01-405977. PMC 3412329. PMID 22529291.CS1 maint: PMC format (link)